Abstract Introduction Cancer incidence and mortality estimates for 25 cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for the European Union (EU-27) ...for 2012. Methods We used statistical models to estimate national incidence and mortality rates in 2012 from recently-published data, predicting incidence and mortality rates for the year 2012 from recent trends, wherever possible. The estimated rates in 2012 were applied to the corresponding population estimates to obtain the estimated numbers of new cancer cases and deaths in Europe in 2012. Results There were an estimated 3.45 million new cases of cancer (excluding non-melanoma skin cancer) and 1.75 million deaths from cancer in Europe in 2012. The most common cancer sites were cancers of the female breast (464,000 cases), followed by colorectal (447,000), prostate (417,000) and lung (410,000). These four cancers represent half of the overall burden of cancer in Europe. The most common causes of death from cancer were cancers of the lung (353,000 deaths), colorectal (215,000), breast (131,000) and stomach (107,000). In the European Union, the estimated numbers of new cases of cancer were approximately 1.4 million in males and 1.2 million in females, and around 707,000 men and 555,000 women died from cancer in the same year. Conclusion These up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe. The important role of cancer registries in disease surveillance and in planning and evaluating national cancer plans is becoming increasingly recognised, but needs to be further advocated. The estimates and software tools for further analysis (EUCAN 2012) are available online as part of the European Cancer Observatory (ECO) ( http://eco.iarc.fr ).
Background: Worldwide, female melanoma patients have superior survival compared with males, which is usually ascribed to earlier detection among women and/or a more favorable site distribution. We ...studied gender difference in melanoma survival in a large population-based setting after adjusting for tumor-related variables and offer clues for further research. Patients and methods: A total of 10 538 patients diagnosed with melanoma from 1993 to 2004 in The Netherlands were included. Multivariate analyses were carried out to estimate adjusted relative excess risk (RER) of dying for men compared with women, adjusted for the patient and tumor characteristics. Results: Univariate relative survival analyses showed a RER of dying of 2.70 95% confidence interval (CI) 2.38–3.06 for men compared with women. After adjusting for time period of diagnosis, region, age, Breslow thickness, histologic subtype, body site, nodal and metastatic status, a significant excess mortality risk was still present for males (RER 1.87, 95% CI 1.65–2.10). Among patients with advanced disease and in those <45 or ≥60, the adjusted risk estimates were similar. Conclusions: The superior survival of women compared with men persisted after adjusting for multiple confounding variables indicating that factors other than stage at diagnosis and body site reduce mortality risk in female melanoma patients.
Current normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and ...validation of gene signatures. Most studies on optimization of normalization methods typically use simulated data to validate methodologies. We describe a new method, GeTMM, which allows for both inter- and intrasample analyses with the same normalized data set. We used actual (i.e. not simulated) RNA-seq data from 263 colon cancers (no biological replicates) and used the same read count data to compare GeTMM with the most commonly used normalization methods (i.e. TMM (used by edgeR), RLE (used by DESeq2) and TPM) with respect to distributions, effect of RNA quality, subtype-classification, recurrence score, recall of DE genes and correlation to RT-qPCR data.
We observed a clear benefit for GeTMM and TPM with regard to intrasample comparison while GeTMM performed similar to TMM and RLE normalized data in intersample comparisons. Regarding DE genes, recall was found comparable among the normalization methods, while GeTMM showed the lowest number of false-positive DE genes. Remarkably, we observed limited detrimental effects in samples with low RNA quality.
We show that GeTMM outperforms established methods with regard to intrasample comparison while performing equivalent with regard to intersample normalization using the same normalized data. These combined properties enhance the general usefulness of RNA-seq but also the comparability to the many array-based gene expression data in the public domain.
Abstract Background Survival of gastric cancer in the Western world remains poor. We conducted a retrospective population-based study to evaluate trends in incidence, treatment and outcome of gastric ...adenocarcinoma. Methods All patients diagnosed with gastric adenocarcinoma during 1990–2007 in the Dutch Eindhoven Cancer Registry area were included ( n = 4797). Trend analyses were conducted for incidence, mortality, tumour and patient characteristics, treatment and crude overall survival, according to tumour location (cardia versus non-cardia). Temporal changes in the odds of undergoing surgery and the risk of death were analysed by means of multivariable regression methods. Results Age-standardised incidence decreased among males (24–12 per 100,000 inhabitants) and females (10–6); mortality rates decreased at a similar pace. The proportion of cardia tumours remained stable. Stage distribution worsened over time among patients with cardia (stages I and II: 32% in 1990–1993 and 22% in 2006–2007, p = 0.005) and non-cardia (stage IV: 33% in 1990–1993 and 40% in 2006–2007, p = 0.0003) cancer. Chemotherapy rates increased in all settings. Five-year survival worsened over time for patients with non-cardia tumours. Age and stage had significant influence on survival after stratification for tumour localisation. After adjustments for relevant factors (i.e. stage), the risk of death decreased since the late 90s for patients with a cardia tumour (hazard ratio 0.8, p = 0.01). Conclusion The absence of improvement in survival rates indicates the need for earlier detection and prospective studies to evaluate new therapy regimens with standardised surgery and pathology.
The associations of socioeconomic status (SES) and participation in the breast cancer screening program, as well as consequences for stage of disease and prognosis were studied in the Netherlands, ...where no financial barriers for participating or health care use exist. From 1998 to 2005, 1,067,952 invitations for biennial mammography were sent to women aged 50–75 in the region covered by the Eindhoven Cancer Registry. Screening attendance rates according to SES were calculated. Tumor stage and survival were studied according to SES group for patients diagnosed with breast cancer between 1998 and 2006, whether screen-detected, interval carcinoma or not attended screening at all. Attendance rates were rather high: 79, 85 and 87% in women with low, intermediate and high SES (
p
< 0.001), respectively. Compared to the low SES group, odds ratios for attendance were 1.5 (95%CI:1.5–1.6) for the intermediate SES group and 1.8 (95%CI:1.7–1.8) for the high SES group. Moreover, women with low SES had an unfavorable tumor-node-metastasis stage compared to those with high SES. This was seen in non-attendees, among women with interval cancers and with screen-detected cancers. Among non-attendees and interval cancers, the socioeconomic survival disparities were largely explained by stage distribution (48 and 35%) and to a lesser degree by therapy (16 and 16%). Comorbidity explained most survival inequalities among screen-detected patients (23%). Despite the absence of financial barriers for participation in the Dutch mass-screening program, socioeconomic inequalities in attendance rates exist, and women with low SES had a significantly worse tumor stage and lower survival rate.
Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the ...Netherlands from 1990 to 2014.
The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival.
Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p < .01). This increase was solely for patients ≥18 months old (3.0–5.4; AAPC +3.3%, p = .01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p < .01 and HR 0.37, p < .01, respectively).
Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy.
•The incidence of stage 4 neuroblastoma increased 2.9% per year between 1990 and 2014.•Five-year overall survival of stage 4 patients improved from 19 ± 6% to 44 ± 6%.•High-dose chemotherapy and immunotherapy contributed most to the improved survival.
Background
Numerous studies have examined prognostic factors for survival of breast cancer patients, but relatively few have dealt specifically with 10+-year survivors.
Methods
A review of the PubMed ...database from 1995 to 2006 was undertaken with the following inclusion criteria: median/mean follow-up time at least 10 years; overall survival and/or disease-specific survival known; and relative risk and statistical probability values reported. In addition, we used data from the long-standing Eindhoven Cancer Registry to illustrate survival probability as indicated by various prognostic factors.
Results
10-year breast cancer survivors showed 90% 5-year relative survival. Tumor size, nodal status and grade remained the most important prognostic factors for long-term survival, although their role decreased over time. Most studies agreed on the long-term prognostic values of MI (mitotic index), LVI (lymphovascular invasion), Her2-positivity, gene profiling and comorbidity for either all or a subgroup of breast cancer patients (node-positive or negative). The roles of age, socioeconomic status, histological type, BRCA and p53 mutation were mixed, often decreasing after correction for stronger prognosticators, thus limiting their clinical value. Local and regional recurrence, metastases and second cancer may substantially impair long-term survival. Healthy lifestyle was consistently related to lower overall mortality.
Conclusions
Effects of traditional prognostic factors persist in the long term and more recent factors need further follow-up. The prognosis for breast cancer patients who have survived at least 10 years is favourable and increases over time. Improved long-term survival can be achieved by earlier detection, more effective modern therapy and healthier lifestyle.
Background
Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they ...are generally not easily accessible.
Objectives
To assess recent age‐ and sex‐specific trends in melanoma incidence and make predictions for 2010 and 2015.
Methods
A retrospective registry‐based analysis was performed with data from 29 European cancer registries. Most of them had data available from 1990 up to 2006/7. World‐standardized incidence rates (WSR) and the estimated annual percentage change (EAPC) were computed. Predictions were based on linear projection models.
Results
Overall the incidence of melanoma is rapidly rising and will continue to do so. The incidence among women in Europe was generally higher than in men. The highest incidence rates were seen for Northern and north‐western countries like the UK, Ireland and the Netherlands. The lowest incidence rates were observed in Portugal and Spain. The incidence overall remained stable in Norway, where, amongst young (25–49 years) Norwegian males rates significantly decreased (EAPC −2.8, 95% CI −3.6; −2.0). Despite a low melanoma incidence among persons above the age of 70, this age group experienced the greatest increase in risk during the study period.
Conclusions
Incidence rates of melanoma are expected to continue rising. These trends are worrying in terms of disease burden, particularly in eastern European countries.
Aims/hypothesis
Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg ...human insulin) is associated with an increased risk of cancer in a large population-based cohort study.
Methods
Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes.
Results
Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose–response relationships could not be identified.
Conclusion/interpretation
Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.
Comorbidity and socioeconomic status (SES) may be related among cancer patients.
Population-based cancer registry study among 72,153 patients diagnosed during 1997-2006.
Low SES patients had 50% ...higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity.
This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions.
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