| 1. |
- Cheng, Wei Kang, et al.
(författare)
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Nuclear and stromal expression of Manic fringe in renal cell carcinoma
- 2021
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Ingår i: Experimental and molecular pathology (Print). - : Elsevier. - 0014-4800 .- 1096-0945. ; 122
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most common type of kidney cancer and has the highest mortality rate among genitourinary cancers. Despite the advances in molecular targeted therapies to treat RCC, the inevitable emergence of resistance has delineated the need to uncover biomarkers to prospectively identify patient response to treatment and more accurately predict patient prognosis. Fringe is a fucose specific beta 1, 3N-acetylglucosaminyltransferase that modifies the Notch receptors. Given the link between its function and aberrant Notch activation in RCC, Fringe may be implicated in this disease. The Fringe homologs comprise of Lunatic fringe (LFng), Manic fringe (MFng) and Radical fringe (RFng). MFng has been reported to play a role in cancer. MFng is also essential in the development of B cells. However, the expression profile and clinical significance of MFng, and its association with B cells in RCC are unknown. CD20 is a clinically employed biomarker for B cells. This pilot study aimed to determine if MFng protein expression can be utilized as a prospective biomarker for therapeutics and prognosis in RCC, as well as to determine its association with CD20+ B cells. Analysis of publicly available MFng gene expression datasets on The Cancer Genome Atlas Netlwork (TCGA) identified MFng gene expression to be up-regulated in Kidney Clear Cell Renal Carcinoma (KIRC) patients. However there was no significant association between the patient survival probability and the level of MFng expression in this cohort. Immunohistochemistry performed on a tissue microarray containing cores from 64 patients revealed an elevated MFng protein expression in the epithelial and stromal tissues of RCC compared to the normal kidney, suggesting a possible role in tumorigenesis. Our study describes for the first time to our knowledge, the protein expression of MFng in the nuclear compartment of normal kidney and RCC, implicating a prospective involvement in gene transcription. At the cellular level, cytoplasmic MFng was also abundant in the normal kidney and RCC. However, MFng protein expression in the malignant epithelial and stromal tissue of RCC had no positive correlation with the patients' overall survival, progression-free survival and time to metastasis, as well as the gender, age, tumor stage and RCC subtype, indicating that MFng may not be an appropriate prognostic marker. The association between CD20+ B cells and epithelial MFng was found to approach borderline insignificance. Nonetheless, these preliminary findings may provide valuable information on the suitability of MFng as a potential therapeutic molecular marker for RCC, thus warrants further investigation using a larger cohort.
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| 2. |
- Cortés-González, Jeff R, et al.
(författare)
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Early salvage radiation therapy combined with short-term hormonal therapy in recurrent prostate cancer after radical prostatectomy: Single-institution 4-year data on outcome, toxicity, health-related quality of life and co-morbidities from 184 consecutive patients treated with 70 Gy.
- 2013
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Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 42:1, s. 109-17
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the role of 70Gy salvage radiotherapy (SRT) combined with short-term neoadjuvant hormonal therapy (NHT) in the treatment of recurrent disease after radical prostatectomy (RP), and to consider quality of life (QoL), survival outcomes and impact of co-morbidities on treatment-related rectal-genitourinary toxicity. Electronic records of 184 SRT patients treated consecutively between October 2001 and February 2007 were analyzed. Median age was 64 years (median follow-up 48months). NHT was given to 165 patients (median 3 months). Pre-RP and pre-SRT PSA, PSA doubling time, Gleason score (GS), seminal vesicle invasion (SVI) and detectable post-SRT PSA were recorded. Any detectable PSA or PSA >0.1 ng/ml + nadir was considered biochemical failure (BcF). The Charlson co-morbidity index was used to correlate co-morbidities and rectal-genitourinary toxicity. Scores from the health-related QoL EORTC QLQ-C30 and PR-25 questionnaires were also evaluated. In 116 (63%) patients, a long-lasting curative effect was indicated by undetectable PSA levels. In univariate analysis, using BcF as an outcome variable, p<0.001 was found for GS, pre-SRT PSA, SVI and detectable post-SRT PSA. Multivariate analysis showed p=0.01 for SVI, p=0.09 for GS, and detectable post-SRT PSA (p=0.01); with metastases as an outcome variable, only SVI was significant (p=0.007). Cancer-specific and overall survival were 99 and 95%, respectively. Although microscopy showed SVI or GS 8-10 in the prostatectomy specimens 17/40(43%) and 13/29 (45%), respectively, of patients still showed undetectable PSA at long-term follow-up (median 55 months) after SRT. Likewise, 11/31 (36%) patients with pre-SRT PSA >1.0 ng/ml and 80/134 (60%) patients with PSA doubling time (PSADT) <10 still showed undetectable PSA after 50 months. Slightly elevated acute and late rectal-genitourinary grade 3-4 toxicity was observed. No association with co-morbidity/toxicity was found. EORTC QLQ-C30 scores were similar to or slightly better than reference values. SRT with 70 Gy combined with 3-month NHT results in long-term undetectable PSA in >50% of patients with recurrence after RP with acceptable rectal-genitourinary toxicity and without negatively affecting long-term QoL. Non-metastatic patients should not be disqualified from receiving SRT although presenting with poor prognostic factors at surgery.
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| 3. |
- Dabestani, Saeed, et al.
(författare)
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Renal cell carcinoma recurrences and metastases in primary non-metastatic patients : a population-based study
- 2016
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Ingår i: World journal of urology. - New York, USA : Springer. - 0724-4983 .- 1433-8726. ; 34:8, s. 1081-1086
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort.Methods: Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis.Results: In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD ± 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention.Conclusions: In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy.
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| 4. |
- Escudier, Bernard, et al.
(författare)
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Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
- 2009
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 27:25, s. 4068-4075
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen. PATIENTS AND METHODS: Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures. RESULTS: One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM. CONCLUSION: Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.
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| 5. |
- Farnebo, Jacob, et al.
(författare)
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Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 408-
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Tidskriftsartikel (refereegranskat)abstract
- Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression-free patient survival. Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression-free survival. Results: Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression-free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Conclusions: Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression-free and overall survival in patients with mRCC.
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| 6. |
- Frödin, Magnus, et al.
(författare)
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Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 116:2, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Background:Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-Angiogenic treatment with multi-Tyrosine-kinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PDGFR-β, as a determinant of prognosis in other tumour types.Methods:This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-Alone-Treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers α-SMA or PDGFR-β.Results:Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-SMA as well as low vessel density was significantly associated with short survival in uni-and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-β perivascular heterogeneity, was also associated with prognosis in uni-And multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer.Conclusions:The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-β. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-Tyrosine-kinase-inhibitors.
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| 7. |
- Harmenberg, Ulrika, et al.
(författare)
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Curative radiation therapy in prostate cancer.
- 2011
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Ingår i: Acta Oncologica. - : Informa Healtcare. - 0284-186X .- 1651-226X. ; 50:Suppl 1, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy has experienced an extremely rapid development in recent years. Important improvements such as the introduction of multileaf collimators and computed tomography (CT)-based treatment planning software have enabled three dimensional conformal external beam radiation therapy (3DCRT). The development of treatment planning systems and technology for brachytherapy has been very rapid as well. Development of accelerators with integrated on-board imaging equipment and technology, for example image-guided radiation therapy (IGRT) has further improved the precision with reduced margins to adjacent normal tissues. This has, in turn, led to the possibility to administer even higher doses to the prostate than previously. Although radiotherapy and radical prostatectomy have been used for the last decades as curative treatment modalities, still there are no randomized trials published comparing these two options. Outcome data show that the two treatment modalities are highly comparable when used for low- and intermediate-risk prostate cancer.
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| 8. |
- Ingvarsson, Johan, et al.
(författare)
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Detection of pancreatic cancer using antibody microarray-based serum protein profiling
- 2008
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Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 8:11, s. 2211-2219
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Tidskriftsartikel (refereegranskat)abstract
- The driving force behind oncoproteomics is to identify protein signatures that are associated with a particular malignancy. Here, we have used a recombinant scFv antibody microarray in an attempt to classify sera derived from pancreatic adenocarcinoma patients versus healthy subjects. Based on analysis of nonfractionated, directly labeled, whole human serum proteomes we have identified a protein signature based on 19 nonredundant analytes, that discriminates between cancer patients and healthy subjects. Furthermore, a potential protein signature, consisting of 21 protein analytes, could be defined that was shown to be associated with cancer patients having a life expectancy of <12 months. Taken together, the data suggest that antibody microarray analysis of complex proteomes will be a useful tool to define disease associated protein signatures.
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| 9. |
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| 10. |
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| 11. |
- Morin, Eric, et al.
(författare)
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Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 250:4, s. 387-396
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium.
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| 12. |
- Redig, Josefine, et al.
(författare)
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Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden : a population-based retrospective analysis
- 2019
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Ingår i: Cancer Management and Research. - Auckland : Dove medical press. - 1179-1322. ; 11, s. 1289-1297
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach.Methods: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002-2005; early TT introduction (TTi), patients diagnosed 2006-2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009-2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period.Results: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi.Conclusion: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.
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| 13. |
- Sjöberg, Elin, et al.
(författare)
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A minority-group of renal cell cancer patients with high infiltration of CD20+B-cells is associated with poor prognosis
- 2018
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 119:7, s. 840-846
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of B-lymphocytes in solid tumours is unclear. Tumour biology studies have implied both anti- and pro-tumoural effects and prognostic studies have mainly linked B-cells to increased survival. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking.METHODS: Following immunohistochemistry (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in an RCC discovery-and validation cohort. Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset.RESULTS: IHC analyses of the discovery cohort identified a previously unrecognised subgroup of RCC patients with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed significantly shorter survival according to uni- and multi-variable analyses. The association between poor prognosis and high density of CD20+ B-cells was confirmed in the validation cohort. Analyses of the KIRC gene expression dataset using the B-cell signature confirmed findings from IHC analyses. Analyses of other gene expression datasets, representing 13 different tumour types, indicated that the poor survival-association of B-cells occurred selectively in RCC.CONCLUSION: This exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.
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| 14. |
- Stenman, Maria, et al.
(författare)
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Albumin, corticosteroid use and Karnofsky performance status predict outcome of single-fraction gamma knife radiosurgery in clear cell renal cell carcinoma patients with brain metastases
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background and Purpose: To evaluate the effects of single fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA).Material and Methods: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n=43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60-100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE).Results: One hundred and ninety-four targets were irradiated. Median number of targets at first sf-GKRS were two. The median prescription dose was 22 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC at 12 and 18 months were 97% and 90%. Median OS from first sf-GKRS was 15.7 months. Serum albumin (HR 5.3), corticosteroids pre sf-GKRS (HR 5.8) and KPS (HR 9.1) were independent prognostic factors. MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases provided no additional prognostic information. Other prognostic scores for BM radiosurgery, including DS-GPA, Renal-GPA, LLV-SIR and CITV-SIR, did not add prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within one month of sf-GKRS.Conclusions: We identified three independent prognostic factors with potential impact on clinical decision making in patients with clear cell RCC BM.
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| 15. |
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| 16. |
- Stenman, Maria, 1987-, et al.
(författare)
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Metastatic papillary renal cell carcinoma in the era of targeted therapy : a retrospective study from three European academic centres
- 2019
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 58:3, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking.PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors.RESULTS: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors.CONCLUSION: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.
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| 17. |
- Stenman, Maria, M.D. 1987-
(författare)
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Treatment selection in metastatic renal cell carcinoma : Towards an individualised approach
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Renal cell carcinoma (RCC), a common malignancy worldwide, affects 1200 new patients yearly in Sweden. Metastatic RCC (mRCC) develops in one in three and is commonly incurable. Clear cell histology dominates followed by papillary histology. The mainstay of mRCC treatment is targeted agents (TA) against aberrantly signalling pro-angiogenic tyrosine kinase receptors, and recently also immune checkpoint inhibitors. Local metastatic therapy with stereotactic radiotherapy (SRT) or surgical metastasectomy may be considered for oligometastatic disease.The aims of this thesis were (1) to identify clinically relevant factors useful for prognostication in real-world patients with mRCC treated in the TA era, (2) to deepen the understanding of papillary mRCC, and (3) to evaluate local metastatic therapy in mRCC. The papers of this thesis were based on retrospective data from regional databases or patient records from 2005 and onwards to reflect the contemporary therapeutic landscape.Paper I was a single-centre study analysing inflammatory blood and clinical parameters in relation to overall survival (OS) in mRCC (n=84). Median OS (mOS) was 20 months. Hypoalbuminemia was a negative prognostic factor (HR 2.7), independently of patient performance status (PS) or Memorial Sloan Kettering Cancer Center risk criteria.Paper II included solely patients with papillary mRCC (n=86) treated at three centres. mOS was 11 months. Age ≥60 years (HR 2.2), ≥3 metastatic sites (HR 2.7), and Eastern Cooperative Oncology Group (ECOG) PS ≥2 vs 1 (HR 3.0) were independently associated with worse OS.Paper III included mRCC patients treated with local metastatic therapy (n=117). Survival was similar irrespective of SRT or surgical metastasectomy with a mOS of 51 months. Treatment with TA in close proximity to local therapy was well tolerated. ECOG PS 1 vs 0 (HR 2.9), intracranial treatment (HR 1.8), and watchful waiting ≥18 months prior to treatment (HR 0.3) were independently prognostic. Paper IV was a follow-up of patients with ccRCC brain metastases treated with single fraction gamma knife radiosurgery (sf-GKRS) at three European centres (n=43). 1- and 3-year local control rates were 97% and 90%, and mOS was 16 months. Hypoalbuminemia (HR=5.3), corticosteroids prior to sf-GKRS (HR=5.8), and Karnofsky PS <80% (HR=9.1) were independently associated with worse OS, whereas previously described prognostic scores were not. Adverse radiation effects (ARE) were uncommon and associated with large target volumes and pre-treatment oedema.In conclusion, this thesis identifies several factors potentially useful for prognostication in mRCC, and indicates the usefulness of local metastatic therapy, in particular SRT, in selected patients. The results should be validated prospectively.
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| 18. |
- Thorstenson, Andreas, et al.
(författare)
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Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden
- 2015
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Ingår i: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- Methodology: Since the start in 2005 virtually all patients with newly diagnosed renal cell carcinoma (RCC) in Sweden are reported to the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence, and survival.Results: A total of 8556 patients with newly diagnosed RCC were registered in the NSKCR from 2005 to 2013 resulting in a coverage of 99% as compared to the Swedish Cancer Registry. The mean tumor size at detection decreased from 70 mm in 2005 to 64 mm in 2010. The proportion of patients who were incidentally detected increased. The proportion of patients with tumor stage T1a who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2012. Similarly, the proportion of laparoscopically performed radical nephrectomies increased from 6% in 2005 to 17% in 2010. During the five years of follow-up 20% of the patients had a recurrence.Conclusion: Over the last decade there has been a trend of earlier detection and less advanced tumors at detection in patients with RCC. An increasing proportion of the patients undergo laparoscopic and nephron-sparing procedures.
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| 19. |
- Thorstenson, Andreas, et al.
(författare)
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Impact of quality indicators on adherence to National and European guidelines for renal cell carcinoma
- 2016
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 50:1, s. 2-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this population-based study was to evaluate the impact of quality indicators on the adherence to guidelines for renal cell carcinoma (RCC).Material and methods: Since 2005, virtually all patients with newly diagnosed RCC in Sweden have been registered in the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence and survival. In addition, a number of quality indicators have been measured in the register aiming to increase the quality of care. The quality indicators are: the coverage of the register, histology reports, preoperative chest computed tomography (CT), partial nephrectomy, laparoscopic surgery, centralization to high-volume hospitals and waiting times.Results: A total of 8556 patients with diagnosed RCC were registered from 2005 to 2013 (99% coverage). In 2013, 99% of the histopathology reports were standardized. The number of patients with preoperatively chest CT increased from 59% in 2005 to 89% in 2013. The proportion of patients with RCC T1aN0M0 who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2013. Similarly, laparoscopic radical nephrectomies increased from 6% in 2005 to 24% in 2013. The median tumour size at detection decreased from 60 mm in 2005 to 55 mm in 2013. The proportion of patients who were incidentally detected increased from 43% in 2005 to 55% in 2013.Conclusions: The data show an improved adherence to the guidelines for RCC as measured by quality indicators and a steady process of earlier detection of patients with RCC.
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