Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors.

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.

Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study.

BACKGROUND: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. METHODS: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000-07 and the corresponding time trends during 1995-2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000-07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern. FINDINGS: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000-07. The overall incidence rose annually by 0.5% (99·8% CI 0·3-0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999-2001 to 2007-09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes. INTERPRETATION: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied. FUNDING: The European Commission (Chafea).

Association between smoking at diagnosis and cause-specific survival in patients with rectal cancer: Results from a population-based analysis of 10,794 cases.

BACKGROUND: Currently, the 5-year survival rate for rectal cancer remains at <60%. The identification of potentially modifiable prognostic factors would be of considerable public health importance. A few studies have suggested associations between smoking and survival in rectal cancer; however, the evidence is inconsistent, and most of these studies were relatively small. In a large population-based cohort study, we investigated whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in rectal cancer and whether the association varies by sex, age, or treatment. METHODS: Rectal cancers (ICD10 C19-20) diagnosed between 1994 and 2012 were abstracted from the National Cancer Registry Ireland and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2012. Multivariable Cox proportional hazards models were used to compare cancer-specific death rates in current smokers, ex-smokers, and never smokers. Subgroup analyses by age at diagnosis, sex, and treatment were conducted. RESULTS: A total of 10,794 rectal cancers were diagnosed. At diagnosis, 25% were current smokers, 24% were ex-smokers, and 51% were never smokers. Compared with never smokers, current smokers had a significantly greater rate of death from cancer (multivariable hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.06-1.24), but ex-smokers did not (HR, 1.02; 95% CI, 0.94-1.11). The association was slightly stronger in men (current versus never smokers: HR = 1.13, 95% CI, 1.02-1.24) than females (HR, 1.05; 95% CI, 0.90-1.23), but the test for interaction was not significant (P = .75). The effect of smoking was not modified by age or receipt of tumor-directed surgery, radiotherapy, or chemotherapy. CONCLUSIONS: Rectal cancer patients who smoke at diagnosis have a statistically significant increased cancer death rate. Elucidation of the underlying mechanisms is urgently required. Cancer 2017;123:2543-50. © 2017 American Cancer Society.

Interventions for raising breast cancer awareness in women.

BACKGROUND: Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional. OBJECTIVES: To assess the effectiveness of interventions for raising breast cancer awareness in women. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization's International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) focusing on interventions for raising women's breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s). DATA COLLECTION AND ANALYSIS: Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods. MAIN RESULTS: We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group). Knowledge of breast cancer symptomsIn the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women's awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD -0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness. Knowledge of age-related riskIn the first study, women's knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women's perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD -0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted. Frequency of Breast CheckingIn the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women's breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045). Breast Cancer AwarenessWomen's overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates. AUTHORS' CONCLUSIONS: Based on the results of two RCTs, a brief intervention has the potential to increase women's breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted.

Posttransplant Lymphoproliferative Disorders in Irish Renal Transplant Recipients: Insights From a National Observational Study.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients. METHODS: Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population. RESULTS: We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified. CONCLUSIONS: We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.

Improving prognosis for patients with hepatocellular carcinoma in Ireland 1994-2008.

OBJECTIVES: The incidence of hepatocellular carcinoma (HCC) is increasing in low-prevalence countries such as the USA, UK and Ireland. Over the past two decades, diagnostic techniques have improved and new treatments have been introduced. The aim of this study was to determine whether there has been an impact on hepatoma mortality in Ireland. METHODS: Anonymized cancer registration data from the National Cancer Registry of Ireland were used to investigate patient characteristics and trends in treatment and survival for Irish patients diagnosed with histologically confirmed HCC between 1994 and 2008. Analyses were carried out according to sex, age, stage of disease treatment received and period of incidence. RESULTS: The incidence of HCC in Ireland increased steadily from 1994 to 2008. The median overall survival was 580 days for the entire cohort, with 1, 2, 3 and 5-year survivals of 56, 46, 39 and 36%, respectively. One-year cause-specific survival improved from 38% during 1994-1998, to 51% during 1999-2002 and to 66% during 2003-2007. Five-year cause-specific survival also improved over time from 19 to 34 to 38%, respectively. Surgery was associated with 1, 2, 3 and 5-year survivals of 92, 82, 78 and 78%, respectively. CONCLUSION: This is the first population-based report of incidence, treatment patterns and outcomes of HCC in Ireland. Prognosis improved over time in this biopsy-proven cohort of patients with HCC. This improvement in survival seemed to be largely because of the effect of surgical interventions.

Affluence and Private Health Insurance Influence Treatment and Survival in Non-Hodgkin's Lymphoma.

BACKGROUND: The aim of this study was to investigate inequalities in survival for non-Hodgkin's lymphoma (NHL), distinguishing between direct and indirect effects of patient, social and process-of-care factors. METHODS: All cases of NHL diagnosed in Ireland in 2004-2008 were included. Variables describing patient, cancer, stage and process of care were included in a discrete-time model of survival using Structural Equation Modelling software. RESULTS: Emergency admissions were more common in patients with co-morbid conditions or with more aggressive cancers, and less frequent for patients from more affluent areas. Aggressive morphology, female sex, emergency admission, increasing age, comorbidity, treatment in a high caseload hospital and late stage were associated with increased hazard of mortality. Private patients had a reduced hazard of mortality, mediated by systemic therapy, admission to high caseload hospitals and fewer emergency admissions. DISCUSSION: The higher rate of emergency presentation, and consequent poorer survival, of uninsured patients, suggests they face barriers to early presentation. Social, educational and cultural factors may also discourage disadvantaged patients from consulting with early symptoms of NHL. Non-insured patients, who present later and have more emergency admissions would benefit from better access to diagnostic services. Older patients remain disadvantaged by sub-optimal treatment, treatment in non-specialist centres and emergency admission.

HR+/Her2- breast cancer in pre-menopausal women: The impact of younger age on clinical characteristics at diagnosis, disease management and survival.

Young women (20-39 years-old) with breast cancer are diagnosed with more aggressive tumours and consequently have poorer survival. However, there is an evidence gap as to whether age has an independent effect on survival of pre-menopausal women diagnosed with HR+/Her2- tumours. The aim of this population-based study was to compare characteristics at diagnosis, determinants of treatment and survival in women aged 20-39 and 40-49 years diagnosed with HR+/Her2- tumours. From the National Cancer Registry Ireland, we identified women aged 20-49 diagnosed with a first invasive HR+/Her2- breast cancer during 2002-2008. Women aged 20-39 were compared to those aged 40-49 years. Poisson regression with robust error variance was used to explore the impact of age on treatment receipt. Associations between age and survival from all causes was investigated using Cox models. In multivariate models, women aged 20-39 significantly more often having no cancer-directed surgery (IRR=1.49, 95%CI 1.07, 2.08). In those having surgery, younger age was associated with significantly higher likelihood of receiving chemotherapy; age was not associated with receipt of adjuvant radiotherapy or endocrine therapy. Women aged 20-39 undergoing surgery were significantly more likely to die than women aged 40-49 (HR=1.84, 95%CI: 1.31, 2.59). Age is an independent prognostic factor in younger women diagnosed with HR+/Her2- breast cancer, supporting the hypothesis that breast cancer in women under 40 has more aggressive behaviour, even within HR+/Her2- tumours. Future research should explore the reasons for poorer survival in order to inform strategies to improve outcomes in this age group.

Causes and outcomes of emergency presentation of rectal cancer.

Emergency presentation of rectal cancer carries a relatively poor prognosis, but the roles and interactions of causative factors remain unclear. We describe an innovative statistical approach which distinguishes between direct and indirect effects of a number of contextual, patient and tumour factors on emergency presentation and outcome of rectal cancer. All patients diagnosed with rectal cancer in Ireland 2004-2008 were included. Registry information, linked to hospital discharge data, provided data on patient demographics, comorbidity and health insurance; population density and deprivation of area of residence; tumour type, site, grade and stage; treatment type and optimality; and emergency presentation and hospital caseload. Data were modelled using a structural equation model with a discrete-time survival outcome, allowing us to estimate direct and mediated effects of the above factors on hazard, and their inter-relationships. Two thousand seven hundred and fifty patients were included in the analysis. Around 12% had emergency presentations, which increased hazard by 80%. Affluence, private patient status and being married reduced hazard indirectly by reducing emergency presentation. Older patients had more emergency presentations, while married patients, private patients or those living in less deprived areas had fewer than expected. Patients presenting as an emergency were less likely to receive optimal treatment or to have this in a high caseload hospital. Apart from stage, emergency admission was the strongest determinant of poor survival. The factors contributing to emergency admission in this study are similar to those associated with diagnostic delay. The socio-economic gradient found suggests that patient education and earlier access to endoscopic investigation for public patients could reduce emergency presentation.

Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

BACKGROUND: A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. METHODS: The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. RESULTS: The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall). In addition to the substantial direct effect of this variable (-0.60), its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12), on the one hand, and hospital caseload, on the other, (-0.10) are of similar size. CONCLUSIONS: The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of Structural Equation Modelling. The authors demonstrate the efficacy of this approach in identifying complex causal pathways that mediate the effects of a socio-economic baseline covariate on the hazard of death from colon cancer. The results show that this approach has the potential to shed light on a class of research questions which is of particular relevance in health research.

Tracheostomy and infection prolong length of stay in hospital after surgery for head and neck cancer: a population based study.

OBJECTIVE: To determine the factors that predict length of stay (LOS) in hospital after head and neck cancer (HNC) surgery for patients treated in public hospitals in Ireland between 2002 and 2010. STUDY DESIGN: Cancer registry data on patients with carcinoma of the oropharynx/larynx were identified and linked with hospital in-patient discharge records. Associations between clinical (e.g., surgery type, neoadjuvant chemoradiation), health service factors, and LOS were investigated by using negative binomial regression. RESULTS: Of the patients diagnosed with HNC, 50% (n = 1651) underwent HNC surgery. Median LOS was 10 days (range: 1-289). Variables associated with prolonged LOS included tracheostomy (neck dissection + tracheostomy versus neck dissection only: incident rate ratio [IRR] 2.66; 95% confidence interval [CI] 2.01-3.50); postoperative infection (IRR 2.26; 95% CI 1.94-2.62); and neoadjuvant radiotherapy (IRR 2.15; 95% CI 1.64-2.82). Advanced stage, gastrostomy, and reconstruction were also associated with prolonged LOS. CONCLUSIONS: Tracheostomy and postoperative infection were associated with prolonged LOS. Further investigation of these modifiable risk factors is warranted.

Which women with breast cancer do, and do not, undergo receptor status testing? A population-based study.

INTRODUCTION: Receptor status determines of breast cancer treatment and prognosis. In a population-based study, we investigated predictors of receptor test receipt. MATERIALS AND METHODS: Invasive breast cancers diagnosed 2006-2008 were abstracted from the National Cancer Registry Ireland. Modified Poisson regression with robust error variance was used to identify socio-demographic, health service and clinical predictors of not undergoing ER, PR or HER2 testing. RESULTS: 7619 breast cancers were included. 7% were not tested for any receptor. 92%, 80% and 86% had oestrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) tests, respectively; 73% were tested for all three. For all three tests, unmarried women were significantly less likely to be tested than married women. Current smokers significantly more often had ER and PR tests. Women treated in a high-volume hospital significantly more often had ER and HER2 tests. CONCLUSION: After adjusting for clinical factors, socio-demographic and service-related factors significantly predicted receptor test receipt. Some factors deserve further investigation, especially marital status. In the interests of equity, the reasons underlying these associations should be further investigated.

EUROCOURSE lessons learned from and for population-based cancer registries in Europe and their programme owners: Improving performance by research programming for public health and clinical evaluation.

UNLABELLED: Population-based cancer registries (CRs) in Europe have played a supportive, sometimes guiding, role in describing geographic variation of cancer epidemics and comparisons of oncological practice and preventive interventions since the 1950s for all types of cancer, separate and simultaneously. This paper deals with historical and longitudinal developments of the roughly 160 CRs and their programme owners (POs) that emerged since 1927 and accelerating since the late 70s especially in southern and continental Europe. About 40 million newly diagnosed patients were recorded since the 1950s out of a total of 100 million of whom almost 20 million are still alive and about 10% annually dying from cancer. The perception of unity in diversity and suboptimal comparability in performance and governance of CRs was confirmed in the EUROCOURSE (EUROpe against cancer: Optimisation of the Use of Registries for Scientific Excellence in research) European Research Area (ERA)-net coordination FP7 project of the European Commission (EU) which explored best practices, bottlenecks and future challenges of CRs. Regional oncologic and public health changes but also academic embedding of CRs varied considerably, although Anno 2012 optimal cancer surveillance indeed demanded intensive collaboration with professional and institutional stakeholders in two major areas (public health and clinical research) and five minor overlapping cancer research domains: aetiologic research, mass screening evaluation, quality of care, translational prognostics and survivorship. Each of these domains address specific study questions, mixes of disciplines, methodologies, additional data-sources and funding mechanisms. POs tended to become more and more public health institutes, Health ministries, but also comprehensive cancer centres and cancer societies through more and more funding at project or programme basis. POs were not easy to pin down because of their multiple, sometimes competitive (funding) obligations and increasing complexity of cancer surveillance. But they also rather seemed to need guiding principles for Governance of 'their' CR(s) as well as to appreciate value of collaborative research in Europe and shield CRs against unreasonable data protection in case of linkages. Despite access to specialised care related shortcomings, especially of survival cohort studies, European databases for studies of incidence and survival (such as ACCIS and EUREG on the one hand and EUROCARE and RARECARE on the other hand) have proved to be powerful means for comparative national or regional cancer surveillance. Pooling of comparable data will exhibit much instructive variation in time and place. If POs of CRs would consider multinational European studies of risk and prognosis of cancer more to serve their own regional or national interest, then progress in this field will accelerate and lead to more consistent funding from the EU. The current 20 million cancer survivors and their care providers are likely to appreciate more feedback. CONCLUSION: Most CRs remain uniquely able to report on progress against cancer by studies of variation in incidence (in time and place), detection and survival, referral and treatment patterns and their (side) effects in unselected patients, the latter especially in the (very) elderly. Programming and profiling its multiple and diverse clinical and prevention research is likely to promote involvement of public health and clinical stakeholders with a population-based research interest, increasingly patient groups and licensed 'buyers' of oncologic services.

EUROCOURSE recipe for cancer surveillance by visible population-based cancer RegisTrees in Europe: From roots to fruits.

Currently about 160 population-based cancer registries (CRs) in Europe have extensive experience in generating valid information on variation in cancer risk and survival with time and place. Most CRs cover all cancers, but some are confined to specific cancers or to children. They cover 15-55% of the populations in all of the larger member states of the European Union (EU), except the United Kingdom (UK), and 100% coverage in 80% of those with populations below 20 million. The EU FP 7 EUROCOURSE project, which operated in 2009-2013, explored the essential role of CRs in cancer research and public health, and also focused attention on their programme owners (POs) and stakeholders (e.g. cancer societies, oncological professionals, cancer patient groups, and planners, providers and evaluators of cancer care and mass screening). Generally, all CRs depended on their regional and/or national oncological context and were increasingly involved in population-based studies of quality of cancer care, long-term prognosis and quality of life, one third being very active. Within the public health domain, CRs, in addition to describing the variety of environmental and lifestyle-related cancer epidemics, have also contributed actively to aetiologic research by a European databases that showed wide discrepancies in cancer risk and survival across the EU, and in more depth by follow-up of cohorts and recruitment for case-control studies. CRs were also actively contributing to independent evaluation of mass screening as an intervention which affects quality of care and cancer mortality. The potential of CRs for clinical evaluation has grown substantially through interaction with clinical stakeholders and more incidentally biobanks, also with greater involvement of patient groups - with a special focus on elderly patients who generally do not take part in clinical trials. Whereas 25-35% of CRs are active in a range of cancer research areas, the rest have a low profile and usually provide only incidence and survival data. If they are unable to do so because POs and stakeholders do not demand it, they might also be inhibited by data protection restrictions, especially in German and French speaking countries. The value of population-based studies of quality of oncologic care and mass screening and the flawless reputation with regard to data protection of intensively used CRs in the northwest of Europe offered a sharp contrast, although they also follow the 1995 EU guideline on data protection. CRs thus offer a perfect example of what can be done with sensitive and minimal data, also when enriched by linkages to other databases. Intensive use of the data has allowed CR research departments to take on a visible expertise-based profile but a neutral in many public controversies in preventive oncology. Their management and fundability also appeared to benefit from externally classifying the wide array of tumour- or tract-specific intelligence and research activities for the various users in oncology and public health and also patients - who are the source of the data - are better informed. Transparency on what CRs enable may also improve through programmes of research have been deemed essential to our funding POs (ministries, cancer charities, cancer centres or public health institutes) who might benefit from some guidance to - often suboptimal -governance. Therefore, a metaphoric RegisTree has been developed for self-assessment and to clarify CR working methods and domain-specific performance to stakeholders and funding agencies, showing much room for development in many CRs. All in all, CRs are likely to remain unique sources of independent expert information on the burden of cancer, indispensable for cancer surveillance, with increased attention to cancer survivors, up to 4% of the population. Investments in the expanding CR network across Europe offer an excellent way forward for comparative future cancer surveillance with so many epidemiologic and clinical changes ahead.

Interval cancer rates in the Irish national breast screening programme.

OBJECTIVE: To compare interval cancer rates from the Irish breast screening programme, BreastCheck, for the period 2000-2007 with those from other European countries. METHODS: Data from BreastCheck was linked to National Cancer Registry breast cancer registrations, to calculate numbers of women screened, screen-detected cancers, and interval cancers, by year of screening, in the first and second years after screening, and by initial or subsequent screen. Estimated underlying cancer incidence from the period 1996-1999 inclusive was used to calculate proportionate incidence. We calculated the interval cancer ratio as an alternative measure of the burden of interval cancers. RESULTS: There were 372,658 screening records for 178,147 women in the period 2000-2007. The overall interval rate was 9.6 per 10,000 screens. In the first year after screening, the interval cancer rate was 5.8 per 10,000 screens and this increased to 13.4 in the second year after screening. The screen detection rate for the period was 53.6 per 10,000 screened for all screens combined. Initial screens produced a higher detection rate at 66.9 per 10,000 screened compared with subsequent screens with a screen-detected rate of 41.4 per 10,000 screens. CONCLUSION: Interval breast cancer rates for the first years of the programme are within acceptable limits and are comparable with those in other European programmes. Nationwide roll-out together with the adoption of digital mammography may have an impact on interval cancer rates in future years.

Association of CYP3A variants with kidney transplant outcomes.

Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPARα, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation.

The European Cancer Observatory: A new data resource.

Population-based cancer registries provide indispensable information on cancer incidence and survival, which cannot be obtained by any other means. It is clear that complete and effective use of these data is essential for cancer control, but sharing this information in a uniform, timely and user-friendly manner has been somewhat limited up to now. The European Cancer Observatory (ECO, http://eco.iarc.fr) has been developed in the framework of the EUROCOURSE project (EUROpe against Cancer: Optimisation of Use of Registries for Scientific Excellence in Research) as a comprehensive resource combining all the information currently available in Europe on cancer incidence, mortality, survival and prevalence. The website provides analytical and presentation tools to examine national estimates for 2012 in 40 European countries (EUCAN), data for 130 national or sub-national areas covered by cancer registries for up to 60 years, until 2011 (EUREG) and a planned mechanism for data download (European Cancer Incidence and Mortality (EUROCIM)). The generated statistics outline the considerable variability across Europe in the rates of all major cancer types and help identify key concerns that need to be addressed by public health policies e.g. the unprecedented rise of lung cancer incidence in women with its full impact expected within a decade or so. The support, maintenance and further development of the ECO website should be a high priority for European cancer policymakers, to continue providing this unique information to health professionals, researchers and the general public in Europe and beyond.

Convergence of decreasing male and increasing female incidence rates in major tobacco-related cancers in Europe in 1988-2010.

INTRODUCTION: Smoking prevalence has been declining in men all over Europe, while the trend varies in European regions among women. To study the impact of past smoking prevalence, we present a comprehensive overview of the most recent trends in incidence, during 1988-2010, in 26 countries, of four of the major cancers in the respiratory and upper gastro-intestinal tract associated with tobacco smoking. METHODS: Data from 47 population-based cancer registries for lung, laryngeal, oral cavity and pharyngeal, and oesophageal cancer cases were obtained from the newly developed data repository within the European Cancer Observatory (http://eco.iarc.fr/). Truncated age-standardised incidence rates (35-74 years) by calendar year, average annual percentage change in incidence over 1998-2007 were calculated. Smoking prevalence in selected countries was extracted from the Organisation for Economic Co-operation and Development and the World Health Organization databases. RESULTS: There remained great but changing variation in the incidence rates of tobacco-related cancers by European region. Generally, the high rates among men have been declining, while the lower rates among women are increasing, resulting in convergence of the rates. Female lung cancer rates were above male rates in Denmark, Iceland and Sweden (35-64 years). In lung and laryngeal cancers, where smoking is the main risk factor, rates were highest in central and eastern Europe, southern Europe and the Baltic countries. Despite a lowering of female smoking prevalence, female incidence rates of lung, laryngeal and oral cavity cancers increased in most parts of Europe, but were stable in the Baltic countries. Mixed trends emerged in oesophageal cancer, probably explained by differing risk factors for the two main histological subtypes. CONCLUSIONS: This data repository offers the opportunity to show the variety of incidence trends by sex among European countries. The diverse patterns of trends reflect varied exposure to risk factors. Given the heavy cancer burden attributed to tobacco and the fact that tobacco use is entirely preventable, tobacco control remains a top priority in Europe. Prevention efforts should be intensified in central and eastern Europe, southern Europe and the Baltic countries.

Socioeconomic disparity in survival after breast cancer in ireland: observational study.

We evaluated the relationship between breast cancer survival and deprivation using data from the Irish National Cancer Registry. Cause-specific survival was compared between five area-based socioeconomic deprivation strata using Cox regression. Patient and tumour characteristics and treatment were compared using modified Poisson regression with robust variance estimation. Based on 21356 patients diagnosed 1999-2008, age-standardized five-year survival averaged 80% in the least deprived and 75% in the most deprived stratum. Age-adjusted mortality risk was 33% higher in the most deprived group (hazard ratio 1.33, 95% CI 1.21-1.45, P<0.001). The most deprived groups were more likely to present with advanced stage, high grade or hormone receptor-negative cancer, symptomatically, or with significant comorbidity, and to be smokers or unmarried, and less likely to have breast-conserving surgery. Cox modelling suggested that the available data on patient, tumour and treatment factors could account for only about half of the survival disparity (adjusted hazard ratio 1.18, 95% CI 0.97-1.43, P = 0.093). Survival disparity did not diminish over time, compared with the period 1994-1998. Persistent survival disparities among Irish breast cancer patients suggest unequal use of or access to services and highlight the need for further research to understand and remove the behavioural or other barriers involved.