| 1. |
- Dobilas, Arturas, et al.
(författare)
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Preoperative circulating tumor DNA level is associated to poor overall survival in patients with ovarian cancer
- 2022
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X. ; 32:Suppl 2, s. 405-405
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Konferensbidrag (refereegranskat)abstract
- Introduction/BackgroundCirculating tumor DNA (ctDNA), which is shed from tumor cells into the blood, is a promising minimal-invasive method for cancer diagnostics and monitoring. The aim of this study was to evaluate preoperative ctDNA levels in the plasma of patients with ovarian cancer and correlate the levels to clinico-pathological parameters and patient outcome.MethodologyTumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/mL and variant allele frequency.ResultsSomatic mutations were found in 24 tumors, of which seven were from patients with borderline, and 17 with invasive cancer diagnosis. TP53 was the most frequently mutated gene. Fifteen of 24 patients had detectable ctDNA levels in pre-operative plasma. Plasma ctDNA mutant concentration increased with higher stage (p_trend
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| 2. |
- Dobilas, Arturas, et al.
(författare)
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Preoperative ctDNA Levels Are Associated With Poor Overall Survival in Patients With Ovarian Cancer
- 2023
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Ingår i: Cancer Genomics & Proteomics. - 1790-6245. ; 20:6 suppl, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis.PATIENTS AND METHODS: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency.RESULTS: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008).CONCLUSION: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis.
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| 3. |
- Elenis, Evangelia, 1983-, et al.
(författare)
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Access to infertility evaluation and treatment in two public fertility clinics and the reasons for withholding it : A prospective survey cohort study of healthcare professionals
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Study the proportion of patients affected by involuntary childlessness who are denied fertility treatment and the reasons behind this in a publicly funded healthcare system. Design Survey study using prospectively collected information by healthcare professionals. Setting Two university-affiliated fertility clinics in Sweden. Participants Single women and couples in heterosexual and homosexual relationships seeking fertility evaluation and treatment between November 2017 and April 2018 (943 individual cases). Primary and secondary outcome measures Number and proportion of individuals who were either denied, delayed or granted fertility treatment directly. Furthermore, the reasons behind delaying or completely withholding treatment. Results The majority of those seeking evaluation were heterosexual couples (75%), while 14% were single women and 7.5% were same-sex couples. The great majority of those undergoing evaluation were granted treatment either directly (85%) or after in-depth evaluation (7.5%), while 7.5% were denied treatment. Among those who were denied treatment, there were a greater proportion of single women and couples seeking treatment with donated gametes. Among heterosexual couples, gamete origin was not associated with treatment refusal. Although age did not differ between those granted and denied treatment, a higher body mass index (in both recipient and partner, when applicable) was observed among those being refused treatment. Fertility specialists in Sweden focused their assessment on parental factors that may indirectly entail a risk of harm to the future child, such as medical and psychiatric conditions of the individuals involved, their financial constraints and other social reasons, substance abuse and female obesity. Conclusion Being single or receiving treatment with donated gametes can both be reasons for withholding fertility treatment. Although difficult to operationalise, parenting assessment in Sweden is employed interchangeably in treatments with donated gametes (legally mandated assessment) and even autologous gametes (non-legally mandated assessment) - making evident a need for clear official policy guidelines regulating these assessments and the provision of treatment.
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| 4. |
- Leandersson, Pia, et al.
(författare)
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A Biomarker Panel Increases the Diagnostic Performance for Epithelial Ovarian Cancer Type I and II in Young Women
- 2016
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 36:3, s. 957-965
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: To assess preoperative blood levels of a biomarker panel in relation to the new classification system of epithelial ovarian cancer (EOC) type I and II. Patients and Methods: Preoperative plasma levels of B7-family protein homolog 4 (B7-H4), intact and cleaved soluble urokinase plasminogen activator receptor (suPAR), human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) were analyzed in 350 patients with adnexal lesions. Results: The levels of suPAR(II-III), HE4, CA125 were all higher in EOC II than in EOC I, borderline and benign ovarian tumors. B7-H4 was increased in EOC II compared with benign ovarian tumors. The combination of suPAR(II-III), HE4, CA125 and age in premenopausal women discriminates EOC and borderline tumors from benign tumors to higher accuracy compared to the Risk of Ovarian Malignancy Algorithm (p=0.007). Conclusion: The biomarker panel suPAR(II-III), HE4, CA125 and age in premenopausal women improved discrimination of malignant and benign ovarian tumors. The plasma levels of B7-H4 were increased in patients with EOC II compared to those with benign ovarian tumors.
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| 5. |
- Leandersson, Pia, et al.
(författare)
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Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960–2014 : A population-based cohort study
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014. Methods: A nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology. Results: Overall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS. Conclusions: Survival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.
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| 6. |
- Leandersson, Pia
(författare)
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Ovarian cancer. Biomarkers, surgical outcome and survival.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian cancer is the eighth most common female cancer worldwide and the most lethal of the gynaecologic malignancies. Around 700 women are diagnosed in Sweden per year. Due to vague symptoms most of the patients are diagnosed with late-stage epithelial ovarian cancer (EOC) and prognosis is poor, with a five-year survival of 49%. However, for early-stage EOC the prognosis is excellent. Biomarkers for screening and early diagnosis have been sought for decades. To date, CA125 and HE4 are the only biomarkers in clinical use. Both lack sensitivity and specificity for early-stage EOC. The standard treatment for EOC is primary surgery with adjuvant chemotherapy. Centralisation of ovarian cancer care to high-volume hospitals with subspecialist surgeons and improved chemotherapy regimens have improved outcome and survival. Ovarian cancer surgery was centralised in Sweden in 2012.The aims of my thesis were to assess new biomarkers for their potential to improve the diagnostic performance of CA125 and HE4 in women with ovarian tumours (studies I and II), to evaluate ovarian cancer surgery after centralisation (study III) and to assess the incidence and survival in EOC in Sweden since the 1960s (study IV). Study I: CA125, HE4, B7-H4 and cleaved and intact suPAR were analysed in preoperative plasma samples from 350 women with ovarian tumours. Plasma levels of CA125, HE4 and suPAR(II-III) were found to increase from benign tumours to borderline, EOC type I and EOC type II while B7-H4 was only elevated in EOC II. Logistic regression models were fitted and a model combining CA125, HE4, suPAR(II-III) and age performed better (AUC=0.933) than the established ROMA algorithm (CA125, HE4 and menopause status) for discrimination of benign tumours from EOC in premenopausal women. The ROMA performed best in postmenopausal women (AUC=0.914). Furthermore, we correlated preoperative biomarker levels with survival after EOC diagnosis. High HE4, CA125 and suPAR(I) were prognostic for poor survival. At 12 months suPAR(I) was the only independent biomarker prognostic for poor short-term survival. In women above 75 years, high suPAR(I) indicated very poor prognosis in the first year after diagnosis (HR=8.9, p=0.01).Study II: 177 inflammation- and cancer-associated biomarkers were analysed in preoperative plasma samples from 180 women with ovarian tumour, using the proximity extension assay. HE4 was the best performing single biomarker for discrimination between benign tumours and EOC. Three-biomarker combinations of HE4, CA125 and one additional biomarker were compared to a reference model of HE4 and CA125. No biomarker significantly improved the diagnostic performance of HE4 and CA125. Study III: We analysed data from the GynOp Registry 2013-15. Out of 1108 cases of ovarian cancer surgery with curative intent, 30% were performed in regional hospitals with fewer than 20 cases per year. Four tertiary centres performed more than 25 surgeries per year. Compared with regional hospitals, tertiary centres perform more extensive surgery without an increased frequency of major complications. Large differences exist in patient selection for primary surgery and complete resection rates between the tertiary centres. Study IV: We identified all women with a diagnosis of epithelial ovarian, fallopian tube, and peritoneal cancers or undesignated abdominal/pelvic cancer from 1960 to 2014 in the Swedish Cancer Registry. Analyses of age-standardised incidence and relative survival (RS) were carried out and time trend graphs were modelled according to age, tumour site, and morphology. Since 1980 the age-standardised incidence of EOC has declined in Sweden. The age-standardised RS in EOC up to five years from diagnosis improved from 1960 to 2014. The 10-year RS has remained unchanged since 1960. In conclusion, CA125 plus HE4 continues to stand out as the best biomarker combination for assessment of cancer risk in a woman with ovarian tumours. CA125, HE4 and suPAR(I) are potential prognostic markers. Adding biomarkers to the preoperative assessment, especially in elderly women, could aid in the treatment decision on extensive primary surgery or neoadjuvant treatment. After centralisation of ovarian cancer surgery in Sweden, many women still have surgery at low-volume regional hospitals. The treatment for advanced EOC seems to differ considerably between the tertiary centres. Further centralisation as well as increased collaboration and exchange of knowledge between tertiary centres are needed to ensure equal access to care, regardless of region of living. Improved surgical and oncological treatment has prolonged life after EOC diagnosis. However, long-term survival remains poor. Most patients will die of their cancer. In order to cure EOC we need to find the patients at early stages. Better diagnostic tools are urgently needed.
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| 7. |
- Leandersson, Pia, et al.
(författare)
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Ovarian Cancer Surgery : a Population-based Registry Study
- 2017
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 37:4, s. 1837-1845
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: To evaluate ovarian cancer surgery in tertiary centers (TC) and regional hospitals (RH). Patients and Methods: Data from the GynOp registry on patients undergoing surgery for ovarian cancer or borderline tumor from 2013 to 2015 were analyzed. Results: Four TC and 21 RH reported 1,108 cases of surgery with curative intent, 770 cases (69.5%) in TC and 338 cases (30.5%) in RH. Out of 458 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease 396 (86.5%) had surgery in TC. We found differences in selection for primary debulking surgery (PDS) (45% to 93%, p<0.001) and PDS achieving no residual tumor (36% to 70%, p<0.001) between the four TC. Major complications, re-admissions and re-operation rates did not differ between TC and RH. Conclusion: Tertiary centers perform more extensive surgery compared to regional hospitals without increased frequency of major complications. Tertiary centers display significant differences among patient selection for PDS, as well as achieving no residual tumor.
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| 8. |
- Noer, Mette Calundann, et al.
(författare)
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Confounders other than comorbidity explain survival differences in Danish and Swedish ovarian cancer patients – a comparative cohort study
- 2018
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Ingår i: Acta Oncologica. - 0284-186X. ; 57:8, s. 1100-1108
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Danish ovarian cancer (OC) patients have previously been found to have worse prognosis than Swedish patients, and comorbidity has been suggested as a possible explanation for this survival difference. We aimed to investigate the prognostic impact of comorbidity in surgically treated OC patients in Denmark and Sweden. Methods: This comparative cohort study was based on data from 3118 surgically treated OC patients diagnosed in 2012–2015. The Swedish subcohort (n = 1472) was identified through the Swedish National Quality Register of Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from the Danish Gynecological Cancer Database. The clinical databases have high coverage and similar variables included. Comorbidity was classified according to the Ovarian Cancer Comorbidity Index and overall survival was the primary outcome. Data were analyzed using Kaplan Meier and Cox regression analyses. Multiple imputation was used to handle missing data. Results: We found comparable frequencies of the following comorbidities: Hypertension, diabetes and ‘Any comorbidity’. Arteriosclerotic cardiac disease and chronic pulmonary disease were more common among Swedish patients. Univariable survival analysis revealed a significant better prognosis for Swedish than for Danish patients (HR 0.84 [95% CI 0.74–0.95], p < .01). In adjusted multivariable analysis, Swedish patients had nonsignificant better prognosis compared to Danish patients (HR 0.91 [95% CI 0.80–1.04], p = .16). Comorbidity was associated with survival (p = .02) but comorbidity did not explain the survival difference between the two countries. Conclusions: Danish OC patients have a poorer prognosis than patients in Sweden but the difference in survival seems to be explained by other factors than comorbidity.
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