The current study was designed to determine the risk of cancer in patients with neurofibromatosis type 1 (NF1) by cancer type, age, and sex with unprecedented accuracy to be achieved by combining two ...total population-based registers.
A population-based series of patients with NF1 (N = 1,404; 19,076 person-years) was linked to incident cancers recorded in the Finnish Cancer Registry and deaths recorded in the national Population Register Centre between 1987 and 2012. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for selected cancer types. Survival of the patients with cancer with and without NF1 was compared.
In malignant peripheral nerve sheath tumors and CNS tumors, the cancers traditionally associated with NF1, we observed SIRs of 2,056 (95% CI, 1,561 to 2,658), and 37.5 (95% CI, 30.2 to 46.0), respectively, and SMRs of 2,301 (95% CI, 1,652 to 3,122) and 30.2 (95% CI, 19.1 to 45.2), respectively. We found an unequivocally increased risk for breast cancer. In particular, SIR was 11.1 (95% CI, 5.56 to 19.5) for breast cancer in women with NF1 age < 40 years; the overall SMR for breast cancer was 5.20 (95% CI, 2.38 to 9.88). Particularly high overall SIRs were observed in patients with NF1 age < 15 years: women, 87.6 (95% CI, 58.6 to 125); men, 45.6 (95% CI, 28.4 to 68.5). An estimated lifetime cancer risk for patients with NF1 was 59.6%. The 5-year survival of patients with cancer and NF1, excluding nervous tissue cancers, was worse than that of comparable patients with cancers without NF1 (54.0% v 67.5%; P = .01).
Our results emphasize the general cancer proclivity of patients with NF1. These findings should translate to clinical practices to determine clinical interventions and focused follow-up of patients with NF1.
Purpose To determine which work arrangements, physical working conditions, and psychosocial working conditions are important risk factors for sickness absence. Methods Survey data on working ...conditions collected among the employees of the City of Helsinki during 2000 to 2002 (N = 6503, response rate 67%) were linked to the employer's sickness absence records for the subsequent 3 years. First occurrences of short-term (1−3 days), intermediate (4−14 days), and long-term (15 days or more) sickness absence episodes were examined by the use of proportional hazards models with Bayesian model averaging. Results Working overtime decreased the risk of short-term sickness absence by 19%. Heavy physical work load and hazardous exposures were consistently associated with increased sickness absence episodes of all lengths. The risk of intermediate and long-term absence episodes was increased by 24% to 28% per one standard deviation increase in physical work load. Low job control in women and job dissatisfaction in men increased the risk of sickness absence episodes of all lengths. Conclusions Heavy physical work load and hazardous exposures had the strongest associations with sickness absence. Furthermore, low job control in women and job dissatisfaction in men were consistently associated with increased risk of sickness absence. Systematic differences in risk factors for absence episodes of different lengths were not found.
Introduction Central nervous system (CNS) tumors are a leading cause of cancer-related morbidity and mortality in children. Our aim is to characterize incidence trends of pediatric CNS tumors in ...Finland over the last three decades. Methods Data on all benign and malignant incident CNS tumors diagnosed in children aged 0-14 years in 1990-2017 were extracted from the Finnish Cancer Registry and classified according to the 2016 WHO classification of CNS tumors. We analyzed age-standardized incidence rates (ASR) for pediatric CNS tumors overall and by sex, age, tumor histology, grade, and location using Poisson regression. We used joinpoint regression to evaluate changes in trends. Results Overall, 1117 pediatric CNS tumor cases were registered in Finland with a 1.2:1 male to female ratio. The average annual ASR was 4.3 per 100,000 person-years (95% CI 4.26, 4.34). The most common tumor type was pilocytic astrocytoma (30% of tumors), followed by medulloblastoma (10%) with incidence rates of 1.30 and 0.45 per 100,000 person-years, respectively. The overall incidence of pediatric CNS tumors increased by an annual percentage change (APC) of 0.8% (95% CI 0.2, 1.4). We observed no major changes in incidence trends of tumor histology groups or tumor location groups. The ASR of benign tumors increased by an APC of 1.0 (95% CI 0.1, 2.0). Conclusions Utilizing the high-quality and completeness of data in the Finnish Cancer registry, we found that the incidence of pediatric CNS tumors in Finland has increased slightly from 1990 until 2017. Although variations in diagnostic and registration practices over time might have affected the rates, the trend may also reflect a true increase in incidence. Keywords: Incidence, CNS tumors, Childhood cancer, Trends, Cancer register
Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment ...with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use.
All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables.
One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage.
Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.
Introduction
High hospital case volumes are associated with improved treatment outcomes for numerous diseases. We assessed the association between academic non-profit hospital case volume and ...survival of adult glioblastoma patients.
Methods
From the nationwide Finnish Cancer Registry, we identified all adult (≥ 18 years) patients with histopathological diagnoses of glioblastoma from 2000 to 2013. Five university hospitals (treating all glioblastoma patients in Finland) were classified as high-volume (one hospital), middle-volume (one hospital), and low-volume (three hospitals) based on their annual numbers of cases. We estimated one-year survival rates, estimated median overall survival times, and compared relative excess risk (RER) of death between high, middle, and low-volume hospitals.
Results
A total of 2,045 patients were included. The mean numbers of annually treated patients were 54, 40, and 17 in the high, middle, and low-volume hospitals, respectively. One-year survival rates and median survival times were higher and longer in the high-volume (39%, 9.3 months) and medium-volume (38%, 8.9 months) hospitals than in the low-volume (32%, 7.8 months) hospitals. RER of death was higher in the low-volume hospitals than in the high-volume hospital (RER = 1.19, 95% CI 1.07–1.32, p = 0.002). There was no difference in RER of death between the high-volume and medium-volume hospitals (p = 0.690).
Conclusion
Higher glioblastoma case volumes were associated with improved survival. Future studies should assess whether this association is due to differences in patient-specific factors or treatment quality.
Abstract
Despite the fact that the effect of sex on the occurrence of cancers has been studied extensively, it remains unclear whether sex modifies familial aggregation of cancers. We explored ...sex-specific familial aggregation of cancers in a large population-based historical cohort study. We combined cancer and population registry data, inferring familial relationships from birth municipality-surname-sex (MNS) combinations. Our data consisted of 391,529 incident primary cancers in 377,210 individuals with 319,872 different MNS combinations. Cumulative sex-specific numbers of cancers were compared to expected cumulative incidence. Familial cancer risks were similar between the sexes in our population-wide analysis. Families with concordant cancer in both sexes exhibited similar sex-specific cancer risks. However, some families had exceptionally high sex-specific cumulative cancer incidence. We identified six families with exceptionally strong aggregation in males: three families with thyroid cancer (ratio between observed and expected incidence 184.6; 95% credible interval (95% CI) 33.1–1012.7, 173.4 (95% CI 65.4–374.3), and 161.4 (95% CI 29.6–785.7), one with stomach (ratio 14.4 (95% CI 6.9–37.2)), colon (ratio 15.5 (95% CI 5.7–56.3)) cancers and one with chronic lymphocytic leukaemia (ratio 33.5 (95% CI 17.2–207.6)). Our results imply that familial aggregation of cancers shows no sex-specific preference. However, the atypical sex-specific aggregation of stomach cancer, colon cancer, thyroid cancer and chronic lymphocytic leukaemia in certain families is difficult to fully explain with present knowledge of possible causes, and could yield useful knowledge if explored further.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive ...large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49-16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.
Colorectal cancer (CRC) patient pathways focus typically on periods after confirmed diagnosis and only limited data are available on pathways prior to cancer diagnosis. The aim of the study was to ...describe the use of health services (HS) one year before diagnosis among CRC patients in Finland. We also studied the role of sex, age, stage, and university hospital district in relation to the use of HS during the pre-diagnostic phase. This information is expected to bring light on the question why CRC is often not found in its early stages.
Incident CRC cases (N = 3115) concerning year 2015 were retrieved from the Finnish Cancer Registry and linked with data from the Finnish Institute for Health and Welfare on primary or specialised care outpatient visits or inpatient episodes over one year prior to CRC diagnosis. We modelled the average number of HS events per patient using Poisson regression model with log-link. Change points for monthly HS event rates and 95% CIs one year before diagnosis were evaluated using Poisson broken line regression models.
Around 10% of patients diagnosed in 2015 had no events prior to cancer leaving 2816 CRCs in the study. Of all pre-diagnostic events (N = 23268), 86% were outpatient events and 14% inpatient episodes. More than half of the inpatient episodes (65%) started as urgent admissions. The use of HS started to increase 3-4 months before diagnosis. The average number of pre-diagnostic HS events per patient varied by sex, age, stage and university hospital district. Overall, men had more events per patient than women and older patients had more events than younger patients.
The amount of inpatient episodes starting as urgent admissions indicate potential bottlenecks in the access to health services. An increase in service use only 3-4 months prior to diagnosis reflects a need for advice both for health care professionals and the general population in recognising symptoms of CRC.
Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population‐based ...cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Persons born in 1987–2011 were included, and 524 persons were followed through the files of the Finnish Cancer Registry from birth up to age 20 years. This amounted to 8,376 person years. Fifty‐three patients had cancer <20 years of age, yielding a standardized incidence ratio (SIR) of 35.6. The most frequent location of pediatric cancers was the central nervous system (CNS); there were 45 cases and the SIR was 115.7. Exclusion of 22 optic pathway gliomas (OPGs) gave an SIR of 59.1 for the CNS and 21.6 for all cancers. There were nine malignant peripheral nerve sheath tumors (MPNSTs); their cumulative risk was 2.7% by age 20. No cases of leukemia were observed. NF1 patients showed considerable excess mortality with a standardized mortality ratio (SMR) of 73.1. The survival of NF1 patients with CNS tumors other than OPGs did not differ from that of non‐NF1 controls (HR 0.64, 95% CI 0.23 to 1.76). In conclusion, brain tumors in childhood and MPNSTs in adolescence are malignancies of major concern in patients with NF1. The risk for myeloid malignancies may not be as high as suggested in the literature.
What's new?
Patients with neurofibromatosis type 1 (NF1) are known to have a high risk of various cancers. What has not been well‐studied, however, are the types of cancers that are most common among children with NF1, and how those cancers impact mortality. In this cohort study, the authors found that malignancies do cause increased mortality in patients under age 20. Brain tumors in childhood and malignant peripheral nerve sheath tumors (MPNSTs) in adolescence are of particular concern. On the other hand, the risk of myeloid malignancies may be lower than previously assumed.
Diurnal type (chronotype) differentiates individuals on an axis between the extremes of evening type to morning type. These diurnal-type preferences are thought to be relatively stable, but follow-up ...studies are sparse. The study aims were (1) to compare cross-sectional studies of diurnal type preferences between two decades and (2) to analyze the consistency of diurnal-type preferences using a longitudinal dataset. We analyzed a total of 18 087 adult males from four datasets with information on diurnal type and age. Of these, 2144 were available for survival analysis and 567 for analysis of longitudinal diurnal consistency. Diurnal type was assessed by asking the individual to what extent they would rate themselves a morning or an evening person, categorized into four groups. Statistical tests for stability of diurnal type were based on transition matrices and p values obtained using likelihood ratios. Cox regression was used to calculate the relative risk of all-cause mortality in each of the four diurnal type groups. After direct age standardization, 9.5% (95% CI: 9.0-10.1%) of participants in the four datasets were evening types. The cross-sectional data yielded that morning types were less common in the 2000s than two decades earlier. The longitudinal dataset revealed a significant shift from evening type to another type from 1985 to 2008 (p = 0.002). The relative risk of all-cause mortality was 1.3-fold (95% CI: 1.0-1.6; p = 0.05) higher for evening types compared to morning types. At the population level, eveningness appears to have become more prevalent over recent decades. However, on the individual level, the more morningness the chronotype, the more persistent it remains with aging.
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