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- Andersson-Evelönn, Emma, 1983-
(författare)
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DNA methylation as a prognostic marker in clear cell Renal Cell Carcinoma
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma worldwide. Metastatic ccRCC is correlated to poor prognosis whereas non-metastatic disease has a 5-year survival rate up to 90%. Due to increased accessibility to different types of diagnostic imaging the frequency of metastatic ccRCC at diagnosis has decreased since the beginning of the 21st century. This has led to an earlier detection of primary tumors before patients present symptoms. However, 20-30% of the non-metastatic patients at diagnosis will progress and metastasize within five years of primary nephrectomy. Identifying patients at high risk of tumor progression at an early stage after diagnosis is of importance to improve outcome and survival. Currently, in Sweden, the Mayo scoring system is used to divide tumors into low, intermediate or high risk for tumor progression.DNA methylation has been associated with tumor development and progression in different malignancies. In this thesis, Illumina Infinium HumanMeth27 BeadChip Arrays and Human Meth450K BeadChip Arrays have been used to evaluate the relationship between methylation and clinicopathological variables as well as ccRCC outcome in 45 and 115 patients.Our studies identified an association between higher level of promoter-associated DNA methylation and clinicopathological variables in ccRCC. There was a significant stepwise increase of average methylation from tumor-free tissue, via non-metastatic tumors to metastatic disease. Cluster analysis divided patients into two distinct groups that differed in average methylation levels, TNM stage, Fuhrman nuclear grade, tumor size, survival and tumor progression. We also presented two prognostic classifiers for non-metastatic tumors; the promoter methylation classifier (PMC) panel and the triple classifier. The PMC panel divided tumors depending on the methylation level, PMC low or PMC high, with significantly worse prognosis in the PMC high group. This data was verified in an independent, publically available cohort. The triple classifier was created using a combination of clinicopathological variables, previously identified CpGs biomarkers and a novel cluster analysis approach (Directed Cluster Analysis). The triple classifier had a higher specificity compared to the clinically used Mayo scoring system and predicted tumor progression with higher accuracy at a fixed sensitivity.The identification of two epigenetic classifiers that predicted outcome in non-metastatic ccRCC further establishes the role of DNA methylation as a prognostic marker. This knowledge can contribute to identification of patients with a high risk of tumor progression and can be of importance in the decision regarding adjuvant treatment post-nephrectomy.
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- Bedke, Jens, et al.
(författare)
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The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Immune Checkpoint Inhibitor–based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care
- 2021
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 80:4, s. 393-397
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. Patient summary: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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- Bergerot, Cristiane Decat, et al.
(författare)
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Frustration and distress during treatment for advanced renal cell carcinoma
- 2018
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Ingår i: Journal of Clinical Oncology. - Univ Fed Sao Paulo UNIFESP, Sao Paulo, Brazil. KCCure, Alexandria, VA USA. City Hope Comprehens Canc Ctr, Monrovia, CA USA. Duke Univ, Durham, NC USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Umea Univ, Umea, Sweden. Netherlands Canc Inst, Amsterdam, Netherlands. City Hope Comprehens Canc Ctr, Duarte, CA USA. Ludwig Maximilians Univ Munchen, Univ Hosp Munich Grosshadern, Munich, Germany. City Hope Natl Med Ctr, Duarte, CA USA. : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:34
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Kroger Dahlin, Britt-Inger, et al.
(författare)
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Patient's QoL after open kidney surgery in a randomized study of spinal versus epidural analgesia in patients with renal cell carcinoma
- 2019
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 53, s. 17-17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: This study was aimed to evaluate the patients perspectives, before and one month after surgery in patients treated with open surgery for renal cell carcinoma (RCC). Can effective perioperative analgesia be part of a multimodal approach to minimize morbidity and improve postoperative management [1].Material and Methods: A total of 135 patients with RCC in all stages 2012-2015, were randomized to receive either spinal analgesia with clonidine, or epidural analgesia in addition to the general anesthesia: The patients were stratified according to surgical technique. Inclusion criteria: ASA score I-III, age >18 years, no chronic pain medication or cognitive disorders. The patients survey used was based on the EORTC QLQ-C30. Wilcoxon Signed Rank test and Mann-Whitney-U tests were used for statistical evaluation.Results: A majority of the patients (117 of 135, 86%) responded to the survey. Patients groups treated with partial nephrectomy or radical nephrectomy, had significantly reduced physical and social functioning while emotional functioning improved postoperatively compared with preoperatively. In both surgical groups the patients reported significant negative financial difficulties postoperatively. Similar results was achieved for patients treated with either spinal or epidural anesthesia. The epidural group of patients experienced more negative social functioning but had an improved global health. When comparing the surgical procedures there was no significant difference in the quality of life parameters. However when comparing the analgesic groups, spinal anesthesia had significantly better physical and social functioning after surgery while the patients in the epidural group reported better global health.Conclusion: Patients randomized to be treated with spinal analgesia with clonidine, had better physical and social functioning postoperatively than patients randomized to be treated with epidural analgesia.
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- Ljungberg, Börje, 1949-, et al.
(författare)
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Local recurrence after nephron-sparing therapy in Sweden, a register based study
- 2019
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 53, s. 27-28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: In the Swedish Kidney Cancer Registry 99% of all patients nationwide are reported. The aim of this study is to present results of occurrence of recurrences in the treated kidney after nephron sparing treatments in patients with T1aN0M0 renal cell carcinoma (RCC) and their overall survival.Material: Since 2005 around 14.000 patients have been included prospectively in the National Swedish Kidney Cancer Register. Among those patients there were 5013 out of 5311 patients (94%) without metastatic disease that had a follow-up checkup 5 years after diagnosis. Among the 5013 patients, 39 had unclear recurrence data and were excluded from the analysis. Statistical analysis was done by SPSS 24. SCANDINAVIAN JOURNAL OF UROLOGY 27Results: In total, 1015 (19.9%) had recurrent disease during 5 years follow-up. During the time of diagnosis (2005 -2012,) 1077 patients were treated with nephron sparing treatment: 947 with partial nephrectomy (PN), 114 with radiofrequency ablation (RF) and 16 with other treatments. Among pT1a patients 16 of 712 treated with PN (1.7%) had a local recurrence compared with 13 of 105, (12.3%) RF patients. PN Patients had significantly better overall survival than RF patients. However RF patients were significantly older than PN (67.7 vs 60.6 years, p< 0.0001). Also tumor size was larger in PN (27.3 VS 24.4 MM, P< 0.001) as well as longer follow-up-time 8.1 versus 7.1 years. All PNs had a verified histology while only 97 out of 114 tumors treated with RF had a verified histology (85%).Conclusion: Conclusions. In this population-based study, 19.9% with M0 disease recurred within 5 years. Patients with T1a tumors treated with RF had significantly more frequently local recurrence than PN patients. Furthermore, patients with RF treatment had a significantly shorter overall survival but were older. In contrast, patients treated with PN had larger tumors, had longer follow-up time and were all histology proven. The significance of these observations might be important.
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