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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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- Dahlin, Britt-Inger, et al.
(författare)
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Preoperative carbohydrate drink in a randomized study improves postoperative quality of life after urological surgery.
- 2009
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Ingår i: International Journal of Urological Nursing. - : Wiley Blackwell. - 1749-771X. ; 3:2, s. 64-68
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recently, fast track treatment in surgery has been advocated. Fasting time has been cut down to attenuate preoperative discomfort as irritable and preoperative thirst. We accessed effects of preoperative carbohydrate drink on preoperative quality of life (QOL) including hospitalization time, drinking first day, gut emptying, and return to work. A total of 170 patients scheduled for nephrectomy or prostatectomy were randomized to carbohydrate drink or overnight fasting. Responses a modified QLQ-C30 questionnaire were collected before and one month after surgery. In patients treated with prostatectomy to the variables: did you worry, total health and total QOL improved, while most (19 of 30) variables were impaired. Nephrectomy patients had significantly fewer parameters with impaired QOL than prostatectomy (p = 0.01). There was significant weight loss despite surgical procedure (p < 0.001). When comparing the carbohydrate and control groups, there was no difference concerning age, sex and stages. After prostatectomy, only the QOL variable “worry” improved (p = 0.027) in the carbohydrate group. After nephrectomy, the carbohydrate group had less weight loss (p = 0.035) than controls and had improved QOL as: “short of breath” (p = 0.038), “feel tense” (p = 0.057), “worry” (p = 0.035), and “interfered social activities” (p = 0.024). There was no difference in hospitalization time, drinking 1st day, time to gut emptying, and return to normal activities between the groups, despite surgical procedure. Carbohydrate drink before surgery significantly improved QOL variables such as “worry”, “tense”, and “social activities”. Weight loss was significantly reduced compared with controls after nephrectomy. Thus, carbohydrate drinking before elective surgery improves postoperative QOL parameters, but not postoperative drinking and hospitalization time.
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- Gref, Margareta, 1950-
(författare)
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Glomerular filtration rate in adults : a single sample plasma clearance method based on the mean sojurn time
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glomerular filtration rate (GFR) is a key parameter in evaluating kidney function. After a bolus injection of an exogenous GFR marker in plasma an accurate determination of GFR can be made by measuring the marker concentration in plasma during the excretion. Simplified methods have been developed to reduce the number of plasma samples needed and yet still maintain a high accuracy in the GFR determination. Groth previously developed a single sample GFR method based on the mean sojourn time of a GFR marker in its distribution volume. This method applied in adults using the marker 99m Tc-DTPA is recommended for use when GFR is estimated to be ≥ 30 mL/min. The aim of the present study was to further develop the single plasma sample GFR method by Groth including patients with severely reduced renal function and different GFR markers. Three different GFR markers 51Cr-EDTA, 99mTc-DTPA and iohexol were investigated. Formulas were derived for the markers 51Cr-EDTA and iohexol when GFR is estimated to be ≥ 30 mL/min. For patients with an estimated GFR < 30 mL/min a special low clearance formula with a single sample obtained about 24 h after marker injection was developed. The low clearance formula was proven valid for use with all three markers. The sources of errors and their influence on the calculated single sample clearance were investigated. The estimated distribution volume is the major source of error but its influence can be reduced by choosing a suitable sampling time. The optimal time depends on the level of GFR; the lower GFR the later the single sample should be obtained. For practical purpose a 270 min sample is recommended when estimated GFR ≥ 30 mL/min and a 24 h sample when estimated GFR < 30 mL/min. Sampling at 180 min after marker injection may be considered if GFR is estimated to be essentially normal.
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