| 1. |
- Enroth, Stefan, 1976-, et al.
(författare)
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A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer
- 2018
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Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOver 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.MethodsIn 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).ResultsIn 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 (p=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).ConclusionThe 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.FundingThe Swedish Cancer Foundation, Vinnova (SWELIFE), The Foundation for Strategic Research (SSF), Assar Gabrielsson Foundation.
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| 2. |
- Enroth, Stefan, 1976-, et al.
(författare)
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High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer
- 2019
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 4. |
- Alfonzo, Emilia, et al.
(författare)
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No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study
- 2019
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 116, s. 169-177
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. Patients and methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. Results: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50–2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66–1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. Conclusion: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery. © 2019 The Authors
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| 5. |
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| 6. |
- Berggrund, Malin, et al.
(författare)
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Identification of candidate plasma protein biomarkers for cervical cancer using the multiplex proximity extension assay
- 2019
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 18:4, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared to controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared to population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.
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| 7. |
- Bjurberg, Maria, et al.
(författare)
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Primary treatment patterns and survival of cervical cancer in Sweden : A population-based Swedish Gynecologic Cancer Group Study
- 2019
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Ingår i: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 155:2, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.
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| 8. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
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Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG)
- 2017
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Methods. Nation-wide population-based study of women 18 years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Results. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulldng surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Conclusion. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. (C) 2016 Elsevier Inc. All rights reserved.
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| 9. |
- Falconer, Henrik, et al.
(författare)
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Robot-assisted approach to cervical cancer (RACC) : an international multi-center, open-label randomized controlled trial
- 2019
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29:6, s. 1072-1076
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.
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| 10. |
- Halldorsdottir, Sandra, et al.
(författare)
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Gynecologists are afraid of prescribing hormone replacement to endometrial/ovarian cancer survivors despite national guidelines-a survey in Sweden
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 123:4, s. 225-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prolonged survival in ovarian and endometrial cancer patients increases the importance of paying attention to quality of life. Hormone replacement therapy (HRT) after gynecologic cancer has been controversial. With this survey, we sought to describe Swedish gynecologists’ and gynecologic oncologists’ attitudes towards prescribing HRT to these cancer survivors and see if prescribing practice is consistent with the available evidence and national guidelines.Material and methods: A web-based survey containing three hypothetical cases with a total of 15 questions was distributed to gynecologists and gynecologic oncologists in Sweden. Respondents were asked about their HRT prescription practices in endometrial/ovarian cancer patients with moderate to severe menopausal symptoms.Results: In total 262 gynecologists and 24 gynecologic oncologists answered the survey. In the low-risk endometrial cancer case a majority of the gynecologists (55%) and gynecologic oncologists (66.7%) would prescribe local estrogen. A total of 30% of the gynecologists would prescribe estrogen replacement therapy (ERT) in the high-risk endometrial cancer case compared to 58.3% of the gynecologic oncologists. The gynecologic oncologists felt more comfortable treating patients with endometrial cancer than did gynecologists, and the gynecologists were more likely to read the national guidelines. In the ovarian cancer case, 63.7% of the gynecologists would prescribe HRT compared to 92% of the gynecologic oncologists.Conclusion: Swedish gynecologic oncologists have a more favorable attitude towards HRT for endometrial/ovarian cancer patients and feel more comfortable treating their patients than do gynecologists. This study illustrates a need for education in these matters in order not to withhold HRT from women due to doctors’ sometimes unjustified anxiety.
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