Survival and mortality of elderly men with localized prostate cancer managed with primary androgen deprivation therapy or by primary observation

Background Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment. Methods Men aged >= 70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70-79 years and >= 80 years) and three calendar time cohorts (1985-1994, 1995-2004, and 2005-2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015. Results Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70-79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29-2.23 [1985-1994]; RR 1.55, 95% CI: 1.35-1.84 [1995-2004]; and RR 2.71, 95% CI: 2.08-3.53 [2005-2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age-period interaction = 0.237). Overall survival was also higher among men in their 70's managed by observation compared to those undergoing ADT. Conclusions Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study's conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities

Comparison between the disease-specific Airways Questionnaire 20 and the generic 15D instruments in COPD

<p>Abstract</p> <p>Background</p> <p>Given that the assessment of health-related quality of life (HRQoL) is an essential outcome measure to optimize chronic obstructive pulmonary disease (COPD) patient management, there is a need for a short and fast, reliable and valid instrument for routine use in clinical practice. The objective of this study was to analyse the relationship between the disease-specific Airways questionnaire (AQ20) and the generic 15D health-related quality of life (HRQoL) instrument simultaneously in a large cohort of patients with COPD. We also compare the HRQoL of COPD patients with that of the general population.</p> <p>Methods</p> <p>The AQ20 and 15D were administered to 739 COPD patients representing an unselected hospital-based COPD population. The completion rates and validity of, and correlations among the questions and dimension scores were examined. A factor analysis with varimax rotation was performed in order to find subsets of highly correlating items of the questionnaires.</p> <p>Results</p> <p>The summary scores of AQ20 and 15D were highly correlated (r = - 0.71, p < 0.01). In AQ20 over 50% of patients reported frequent cough, breathlessness during domestic work, and chest problem limiting their full enjoyment of life. 15D results showed a noteworthy decrease of HRQoL in breathing, mobility, sleeping, usual activities, discomfort and symptoms, vitality, and sexual activity (scores ≤ 0.75). Compared to the age- and gender-standardized Finnish general population, the COPD patients were statistically significantly worse off on 13 of 15 dimensions.</p> <p>Conclusions</p> <p>The AQ20 and 15D summary scores are comparable in terms of measuring HRQoL in COPD patients. The data support the validity of 15D to measure the quality of life in COPD. COPD compromises the HRQoL broadly, as reflected by the generic instrument. Both questionnaires are simple and short, and could easily be used in clinical practice with high completion rates.</p

Breast cancer in neurofibromatosis type 1 : overrepresentation of unfavourable prognostic factors

Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P = 0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Estimating multilevel regional variation in excess mortality of cancer patients using integrated nested Laplace approximation

Abstract Models of excess mortality with random effects were used to estimate regional variation in relative or net survival of cancer patients. Statistical inference for these models based on the Markov chain Monte Carlo (MCMC) methods is computationally intensive and, therefore, not feasible for routine analyses of cancer register data. This study assessed the performance of the integrated nested Laplace approximation (INLA) in monitoring regional variation in cancer survival. Poisson regression model of excess mortality including both spatially correlated and unstructured random effects was fitted to the data of patients diagnosed with ovarian and breast cancer in Finland during 1955–2014 with follow up from 1960 through 2014 by using the period approach with five‐year calendar time windows. We estimated standard deviations associated with variation (i) between hospital districts and (ii) between municipalities within hospital districts. Posterior estimates based on the INLA approach were compared to those based on the MCMC simulation. The estimates of the variation parameters were similar between the two approaches. Variation within hospital districts dominated in the total variation between municipalities. In 2000–2014, the proportion of the average variation within hospital districts was 68% (95% posterior interval: 35–93%) and 82% (60–98%) out of the total variation in ovarian and breast cancer, respectively. In the estimation of regional variation, the INLA approach was accurate, fast, and easy to implement by using the R‐INLA package