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- Agnarsdóttir, Margrét, 1970-, et al.
(författare)
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MITF as a Prognostic Marker in Cutaneous Malignant Melanoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Microphthalmia associated transcription factor (MITF) protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma. Methods: A cohort study design based on information collected from population-based registers. For included patients tissue microarrays and immunohistochemistry were employed to study the protein expression of MITF in the primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity. Results: The vast majority of tumors expressed MITF in >25% of the tumor cells with a strong staining intensity and looking at these factors individually these patients had a better prognosis. When cell fraction and intensity were combined a high-risk group dying of malignant melanoma was identified as those with 25% -75% of tumor cells staining with weak intensity and those with <25% of tumor cells staining with strong intensity. However, the majority of the deaths occurred in the lower risk groups. Conclusions: Although a high-risk group for death in malignant melanoma was identified we conclude that MITF is not useful as a prognostic marker because of the distribution of that particular expression in the population. Impact: Our results indicate a bi-phasic pattern of MITF expression and although not useful as a prognostic marker these results are in line with other experimental studies and are relevant to explore further.
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- Lycken, Magdalena, 1973-, et al.
(författare)
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Adherence to guidelines for androgen deprivation therapy after radical prostatectomy : Swedish population-based study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Androgen deprivation therapy (ADT) is a non-curative but essential treatment of prostate cancer with severe side effects. Therefore, both over- and underuse should be avoided. Our aim was to investigate adherence to guidelines for ADT following radical prostatectomy through Swedish population-based data. Methods: We used the database PSA Uppsala/Örebro to study men with localised or locally advanced prostate cancer at diagnosis (clinical stage T1-T3, N0-NX, M0-MX, and prostate-specific antigen (PSA) <50 ng/ml) who underwent radical prostatectomy 1997-2012. Totally 114 men were treated with ADT and selected as cases; 1140 men with no ADT at the index date were selected as controls within four-year strata of time of radical prostatectomy. All men with a PSA doubling time <12 months and/or a biopsy Gleason score of 8-10 were considered to have an indication for ADT according to the European Association of Urology (EAU) guidelines. Results: No indication for ADT was found in 39% of the cases. Among these men, 89% had tumour stage (T-stage) 1-2 at diagnosis, 58% had a biopsy Gleason score 2-6, 98% had an expected remaining lifetime over ten years, 16% received castration, and 84% received antiandrogen monotherapy. Among the controls 5% were found to have an indication for ADT, and 98% of these men had an expected remaining lifetime over ten years.Conclusion: Our results indicate that overtreatment with ADT after radical prostatectomyis common, whereas undertreatment is unusual. Interventions to improve adherence to guidelines are needed to avoid unnecessary side-effects and long treatment durations with ADT.
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- Lycken, Magdalena, 1973-, et al.
(författare)
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Nationwide study of time trends in prostate cancer death over two decades
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Limited data is available to describe the men who die from prostate cancer. Our aim with this study was to describe the time trends for disease characteristics at date of diagnosis, disease duration and age at death for all Swedish men who died from prostate cancer in the period of 1992-2012. Methods:We included all men who died with prostate cancer as the underlying cause of death from 1992 to 2012 according to the Swedish Cause of Death Register. Information on disease characteristics at diagnosis was collected by links to other nation-wide registries through the unique personal identity number. Information on missing data on risk categories for men with an early date of diagnosis was imputed according to the method of chained equations by using R commander. Results: Totally 45 850 men were included. Increased prevalence and decreased age-standardised mortality from prostate cancer was observed during the study period. The proportion of men with localised and locally advanced disease at diagnosis increased from 33% to 46%, while distant metastases decreased from 54% to 42%. Median disease duration increased from 3.1 years (Percentile (P)0.25-P0.75: 1.4-6.0 years) to 5.6 years (P0.25-P0.75: 2.5-9.8 years), and median age at death from prostate cancer increased from 78.3 years (P0.25-P0.75: 72.2-83.4 years) to 81.9 years (P0.25-P0.75: 75.2-87.2 years). The proportion of distant metastases at diagnosis was highest among the youngest men. Conclusion: The longer disease duration and higher age at death may reflect the synergetic effects of prolonged lead time, increased life expectancy, and improvements in the management of prostate cancer during the last two decades.
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| 7. |
- Westerberg, Marcus, et al.
(författare)
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Different assumptions about missingness in registration of metastatic status have important implications for following trends in cancer presentation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: We assessed approaches for handling missing M stage when estimating incidence trends of metastatic prostate cancer at diagnosis (M1) in Sweden. Study design and setting: We used different implementations of deterministic- and multiple imputation to handle missing M stage and estimate the age-standardized incidence of M1. Each method was assessed by studying adjusted survival of men with known and imputed M stage.Results: Missing data in M stage was high (66%) and varied over calendar time and risk groups. The estimated incidence of M1 differed greatly depending on the method of imputation, however all indicated a downward trend. A combination of deterministic imputation and multiple imputation produced adjusted survival curves for men with imputed M stage that best resembled the survival curves for men with known M stage. Conclusions: Deterministic imputation of missing M stage to M0 among men with low risk of metastatic disease in combination with multiple imputation appeared to the best method to estimate incidence of metastatic prostate cancer. Simply substituting missing M stage with M0 most likely underestimates the true incidence of M1. Inclusion of key clinical variables is important to generate plausible imputations. It is important to include data on use of imaging to handle missing M stage appropriately and assess potential bias of a chosen imputation method.
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