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1.
  • Bjurberg, Maria, et al. (författare)
  • Primary treatment patterns and survival of cervical cancer in Sweden : A population-based Swedish Gynecologic Cancer Group Study
  • 2019
  • Ingår i: Gynecologic Oncology. - ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 155:2, s. 229-236
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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 &lt; 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 &lt; 0.001). Stages III-IVA; &lt;40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p &lt; 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.</p>
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2.
  • Bjurberg, Maria, et al. (författare)
  • Primary treatment patterns and survival of cervical cancer in Sweden: A population-based Swedish Gynecologic Cancer Group Study
  • 2019
  • Ingår i: Gynecologic Oncology. - ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 155:2, s. 229-236
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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 amp;lt; 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 amp;lt; 0.001). Stages III-IVA; amp;lt;40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p amp;lt; 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.</p>
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3.
  • Bohr Mordhorst, Louise, 1958-, et al. (författare)
  • Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy
  • 2014
  • Ingår i: Gynecologic Oncology. - Academic Press. - 0090-8258 .- 1095-6859. ; 135:2, s. 305-311
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objective</strong>: Hedgehog signaling proteins were assessed in patients with cervical carcinoma receiving chemoradiation. Associations between five Hedgehog proteins and prognosis were studied.</p><p><strong>Methods</strong>: In all, 131 cases of cervical carcinomas (FIGO stages I-IV) were immunohistochemically (IHC) analyzed for Patched (PTCH), Smoothened (SMO), and GLI1, GLI2 and GLI3 protein expression. Associations between Hedgehog protein expressions, clinicopathological factors, and clinical outcome data were examined.</p><p><strong>Results</strong>: Positive IHC staining for the five Hedgehog proteins was recorded in 8% to 37% of the tumor cells. The highest frequency was noted for SMO and the lowest for all. There was a significant association between low SMO- and GLI2-expression and KRAS-mutation. Tumors with overexpressed SMO had a higher frequency of residual tumor or local recurrences than tumors with low SMO expression. Patients with tumors expressing PTCH in more than 75% of the cells had significantly (P = 0.023) better recurrence-free survival than patients with tumors with low expression. The opposite situation was true for SMO. For GLI2, there was a statistically significant difference with regard to overall (P = 0.004) and distant (P = 0.015) relapse rate for groups with expression of GLI2 in the range of 5-25% compared to higher rates.</p><p><strong>Conclusions</strong>: A predictive and prognostic value was found for PTCH, SMO, and GLI2 with regard to residual carcinoma, local recurrences, and for GLI2 distant relapses. The Hedgehog signaling pathway also seems to play an important role in cervical carcinogenesis together with HPV16-infection and KRAS-mutation.</p>
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4.
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5.
  • Dahm-Kahler, Pernilla, et al. (författare)
  • 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
  • Ingår i: Gynecologic Oncology. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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&lt;0.001), moderate (RR 1.90, P&lt;0.047) and poor differentiation (RR 2.20, P&lt;0.009), neoadjuvant chemotherapy (RR1.33, P&lt;0.022), residual tumor (RR 2.65, P&lt;0.001) and platinum single (2.34, P&lt;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.</p>
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6.
  • Dahm-Kähler, Pernilla, et al. (författare)
  • 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
  • Ingår i: Gynecologic Oncology. - Academic Press. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>OBJECTIVE:</strong> 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.</p><p><strong>METHODS:</strong> Nation-wide population-based study of women≥18years 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.</p><p><strong>RESULTS:</strong> 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 debulking 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&lt;0.001), moderate (RR 1.90, P&lt;0.047) and poor differentiation (RR 2.20, P&lt;0.009), neoadjuvant chemotherapy (RR1.33, P&lt;0.022), residual tumor (RR 2.65, P&lt;0.001) and platinum single (2.34, P&lt;0.001) compared to platinum combination chemotherapy.</p><p><strong>CONCLUSION:</strong> 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.</p>
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7.
  • Fonnes, Tina, et al. (författare)
  • Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions
  • 2018
  • Ingår i: Gynecologic Oncology. - 0090-8258 .- 1095-6859. ; 148:1, s. 197-203
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective</p><p>Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.</p><p>Methods</p><p>782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. <em>ASRGL1</em> mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.</p><p>Results</p><p>Low expression of ASRGL1 protein and <em>ASRGL1</em> mRNA predicted poor disease specific survival (P &lt; 0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04–2.26, P = 0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47–4.74, P = 0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.</p><p>Conclusions</p><p>In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.</p>
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8.
  • Garcia-Dios, Diego A, et al. (författare)
  • High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma.
  • 2013
  • Ingår i: Gynecologic Oncology. - 0090-8258 .- 1095-6859. ; 128:2, s. 327-334
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies. METHODS: Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1063). RESULTS: PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03; P=0.001 for grade 2 and OR=1.89; P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92; P<0.001) and PTEN mutations with type I tumors (OR=19.58; P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38; P=0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18; P=0.028). CONCLUSIONS: Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.
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9.
  • Gyllensten, Ulf, et al. (författare)
  • Primary high-risk HPV screening for cervical cancer in post-menopausal women
  • 2012
  • Ingår i: Gynecologic Oncology. - 0090-8258 .- 1095-6859. ; 125:2, s. 343-345
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective. The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women.</p> <p>Methods. A cohort of post-menopausal women (n =2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement.</p> <p>Results. High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2 + lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% Cl 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population.</p> <p>Conclusions. Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.</p>
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10.
  • Heitz, F., et al. (författare)
  • Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12
  • 2019
  • Ingår i: Gynecologic Oncology. - ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 152:2, s. 235-242
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective. Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. Methods. Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. Results. Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. Conclusions. Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted. (C) 2018 Published by Elsevier Inc.</p>
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