Progress against non-Hodgkin's lymphoma in children and young adolescents in the Netherlands since 1990: Stable incidence, improved survival and lower mortality.

BACKGROUND: With epidemiologic analyses of population-based trends in incidence and outcomes, we ascertained progress against non-Hodgkin's lymphoma (NHL) in children and young adolescents in the Netherlands since 1990. METHODS: Tumour characteristics were extracted from the Netherlands Cancer Registry for patients aged <18 years at diagnosis, between 1990 and 2015. Mortality data for 1980-2016 were derived from Statistics Netherlands. NHL subtypes comprised lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Time trends in incidence and mortality rates and 5-year overall survival (OS) rates were evaluated by average annual percentage change (AAPC) analyses and parametric survival models, respectively. RESULTS: Overall incidence of NHL remained stable at 11 per million person-years (AAPC -0.2%, p = 0.68), with a marked decrease among children of 5-9 years (AAPC -2.6%, p < 0.01), especially among those with BL. Treatment regimens comprised less radiotherapy over time, especially for LBL and BL. Since 2004, most 15-17-year-old patients with NHL have been treated at a paediatric oncology centre. Five-year OS improved from 71% in 1990-94 to 87% in 2010-15 (p < 0.01), the most gain has been achieved in patients with DLBCL and ALCL from 60% and 73%, respectively, to both 90%. Population-based mortality from NHL decreased significantly towards 1.4 per million person-years (AAPC -4.2%, p < 0.01). CONCLUSIONS: This population-based epidemiological study exhibited significant progress against childhood and young adolescent NHL in the Netherlands since 1990, before the advent of a national paediatric oncologic centre in 2018: incidence decreased among children of 5-9 years, survival improved, and mortality steadily decreased over time.

Progress against childhood and adolescent acute lymphoblastic leukaemia in the Netherlands, 1990-2015.

We assessed the epidemiologic progress against childhood and adolescent acute lymphoblastic leukaemia (ALL) in the Netherlands over a 26 year period. ALL patients <18 years were selected from the Netherlands Cancer Registry and the Dutch Childhood Oncology Group. Trend analyses were performed over time and by age group and ALL subtype. Between 1990 and 2015, 2997 ALL patients were diagnosed, i.e. 115 patients (range 87-147) per year. Overall incidence remained stable at 37 per million children, despite increases for B-cell precursor ALL (BCP-ALL) at age 10-14 years (AAPC + 1.4%, p = 0.04) and T-cell ALL at 15-17 years (AAPC + 3.7%, p = 0.01). Five-year survival increased from 80% in 1990-94 to 91% in 2010-15 (p < 0.01). Mortality decreased by 4% annually (p < 0.01). Patients 15-17 years were increasingly treated in a paediatric oncology centre, from 35% in 1990-94 to 87% in 2010-15 and experienced a 70% reduction of risk of death compared to those treated outside such a centre (p < 0.01). Significant progress against childhood ALL has been made in the Netherlands, visible by improved survival rates coinciding with declining mortality rates. These outcomes were accompanied by stable incidence rates, despite increases for BCP-ALL at age 10-14 years and T-cell ALL at age 15-17 years.

Increasing incidence of cancer and stage migration towards advanced disease in children and young adolescents in the Netherlands, 1990-2017.

BACKGROUND: This is the first national study on trends in cancer incidence for children and young adolescents in the Netherlands, including stage at diagnosis as a potential marker of early diagnosis and better staging. METHODS: All neoplasms in patients younger than 18 years, diagnosed between 1990 and 2017 (N = 15,233), were derived from the Netherlands Cancer Registry. Incidence rates and the average annual percentage change with 95% CIs were calculated for all cancers combined and diagnostic (sub)groups. The stability of trends was examined by joinpoint analyses. Potential changes in early detection or improved staging over time were evaluated through proportional alterations in stage at diagnosis. RESULTS: The annual overall cancer incidence increased significantly over time by 0.6% (95% CI 0.3-0.8) from 144 per million person-years in 1990-1999 to 162 in 2010-2017 and was significant for both boys (+0.5%, 0.2-0.8) and girls (+0.7%, 0.3-1.1), for infants (aged 0 years; +1.5%, 0.4-2.5), teenagers (aged 10-14 years; +0.6%, 0.3-1.0) and young adolescents (aged 15-17 years; +0.7%, 0.2-1.2), with no trend interruptions. The incidence of leukaemia (+0.7%, 0.3-1.2), malignant CNS tumours including pilocytic astrocytomas (+1.0%, 0.5-1.5), neuroblastoma (+1.2%, 0.1-2.2) and Ewing bone tumours (+2.4%, 0.9-4.0) increased significantly, whereas temporal variation in trends was observed in boys diagnosed with leukaemia, in pilocytic astrocytoma and malignant melanoma. The proportion of early-stage disease increased in patients with testicular germ cell tumours (+21%) and malignant melanomas (+14%), whereas stage migration towards advanced disease was seen for Hodgkin lymphomas, soft tissue sarcomas and medullary thyroid carcinomas. CONCLUSION: The increasing childhood cancer incidence could not be explained by a rise in early diagnosis, which suggests that background risk factors seem of more importance.

Improved survival for adolescents and young adults with Hodgkin lymphoma and continued high survival for children in the Netherlands: a population-based study during 1990-2015.

Population-based studies that assess long-term patterns of incidence, major aspects of treatment and survival are virtually lacking for Hodgkin lymphoma (HL) at a younger age. This study assessed the progress made for young patients with HL (<25 years at diagnosis) in the Netherlands during 1990-2015. Patient and tumour characteristics were extracted from the population-based Netherlands Cancer Registry. Time trends in incidence and mortality rates were evaluated with average annual percentage change (AAPC) analyses. Stage at diagnosis, initial treatments and site of treatment were studied in relation to observed overall survival (OS). A total of 2619 patients with HL were diagnosed between 1990 and 2015. Incidence rates increased for 18-24-year-old patients (AAPC + 1%, P = 0·01) only. Treatment regimens changed into less radiotherapy and more 'chemotherapy only', different for age group and stage. Patients aged 15-17 years were increasingly treated at a paediatric oncology centre. The 5-year OS for children was already high in the early 1990s (93%). For patients aged 15-17 and 18-24 years the 5-year OS improved from 84% and 90% in 1990-1994 to 96% and 97% in 2010-2015, respectively. Survival for patients aged 15-17 years was not affected by site of treatment. Our present data demonstrate that significant progress in HL treatment has been made in the Netherlands since 1990.

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991-2010 (Automated Childhood Cancer Information System): a population-based study.

BACKGROUND: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991-2010, we provide a consolidated report on cancer incidence trends at ages 0-19 years. METHODS: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991-2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0-14 years) and adolescents (age 15-19 years). We examined and quantified the stability of the trends with joinpoint analyses. FINDINGS: For the years 1991-2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7-138·3) per million person-years and incidence increased significantly by 0·54% (0·44-0·65) per year in children (age 0-14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4-178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73-1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5-47·3) per million person-years and increased significantly by 0·66% (0·48-0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9-24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49-1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65-1·44], malignant CNS tumours in children (average annual change 0·49% [0·20-0·77]), and other tumours in both children (average annual change 0·56 [0·40-0·72]) and adolescents (average annual change 1·17 [0·82-1·53]). INTERPRETATION: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. FUNDING: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer.

Breast cancer in South-Eastern European countries since 2000: Rising incidence and decreasing mortality at young and middle ages.

BACKGROUND: Marked variations exist in the incidence and mortality trends of major cancers in South-Eastern European (SEE) countries which have now been detailed by age for breast cancer (BC) to seek clues for improvement. METHODS: We brought together and analysed data from 14 cancer registries (CRs), situated in SEE countries or directly adjacent. Age-standardised rate at world standard (ASRw) and truncated incidence and mortality rates during 2000-2010 by year, and for four age groups, were calculated. Average annual percentage change of rates was estimated using Joinpoint regression. RESULTS: Annual incidence rates increased significantly in countries and age groups, by 2-4% (15-39 years), 2-5% (40-49), 1-4% (50-69) and 1-6% (at 70+). Mortality rates decreased significantly in all age-groups in most countries, but increased up to 5% annually above age 55 in Ukraine, Serbia, Moldova and Cyprus. The BC data quality was evaluated by internationally agreed indicators which appeared suboptimal for Moldova, Bosnia and Herzegovina and Romania. CONCLUSION: The observed variations of incidence trends reflect the influence of risk factors, as well as levels of early detection activities (screening). While mortality rates were mostly decreasing, probably due to improved cancer care and introduction of more effective systemic treatment regimens, the worrying increasing mortality trends in the 55-plus age groups in some countries have to be addressed by health professionals and policymakers. In order to assess and monitor the effects of cancer control activities in the region, the CRs need substantial investments.

Cigarette smoking-attributable burden of cancer by race and ethnicity in the United States.

PURPOSE: Cigarette smoking is the leading preventable cause of death and disability from cancer in the U.S. Smoking prevalence varies by racial and ethnic group, and therefore the smoking-related burden of cancer is expected to vary accordingly. METHODS: We estimated the cigarette smoking-attributable Disability-Adjusted Life Years (DALYs) lost to cancer, overall and within racial/ethnic groups, using published DALY estimates, smoking prevalence from survey data, and relative risks from large cohort studies. RESULTS: In 2011, 2.6 million DALYs were lost to cancer due to cigarette smoking (27% of all DALYs lost to cancer). Smoking-attributable DALY rates were higher in men (968 per 100,000 people [95% confidence interval: 943-992]) than women (557 [540-574]). In combined sex analyses, DALY rates were higher in non-Hispanic Blacks (960 [934-983]) and non-Hispanic Whites (786 [768-802]) than in Hispanics (409 [399-421]) and non-Hispanic Asians (335 [320-350]). CONCLUSIONS: Smoking-attributable cancer burden was substantial in all racial and ethnic groups, underscoring the need for intensified tobacco cessation in all populations.

Timed Get Up and Go Test and Geriatric 8 Scores and the Association With (Chemo-)Radiation Therapy Noncompliance and Acute Toxicity in Elderly Cancer Patients.

PURPOSE: To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent. METHODS AND MATERIALS: Patients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT. RESULTS: We investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade ≥3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade ≥3, compared with 13% who were not frail. The difference was 7.3% (confidence interval -2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age. CONCLUSIONS: The usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable.

Completeness of Data on Malignant Melanoma Skin Sites and Morphology in the Croatian National Cancer Registry 2000-2014: An Overview of Recent Progress.

Mortality rates and five-year relative survival for malignant melanoma (MM) of the skin in Croatia are poor compared with most European countries. Epidemiological data recorded at the National Cancer Registry (CNCR) are used for informing various decision-makers and researchers, as well as for comparisons with other countries. We analyzed CNCR data on MM skin and morphology for 2000-2007 and 2008-2014 and compared them with European 2000-2007 data. We further stratified skin site analyses in Croatia by sex, different age groups, and sources of reports. We found 52% of case with "non-specified sites" in Croatia in 2000-2007; however, that proportion decreased to 36% in 2008-2014, with 29% of registered MM cases occurring on the trunk, 22% on the limbs, and 13% on the head and neck. The proportion of "non-specified sites" cases in reports originating from university hospitals decreased by 25% and by 9.2% in those from general hospitals. The proportion of "not otherwise specified" among histologically verified cases decreased from 96% in 2000-2007 to 84% in 2008-2014. Our results reveal a substantial proportion of inadequately reported cases, in particular when compared to data at the European level, where in 2000-2007 only 7.7% of cases were from "non-specified sites" and 19% were of non-specified morphology. Irrespective of recent progress, the proportion of unspecified cases still hampers insight into site distribution by subgroups. A further increase in the overall completeness of MM data within CNCR is needed to enable research-informed improvement of melanoma control in the country. Our findings call for engagement of all stakeholders in optimization of the national melanoma registration processes and using models such as RegisTree

U.S. Burden of Cancer by Race and Ethnicity According to Disability-Adjusted Life Years.

INTRODUCTION: In the U.S., people of different races/ethnicities have differences in cancer incidence, mortality, survival, stage at diagnosis, and receipt of treatment, resulting in variances in cancer burden. The burden of cancer in 2011 was assessed by race/ethnicity for 24 cancers using disability-adjusted life years (DALYs). METHODS: In 2014-2015, DALYs and their two components were estimated (years of life lost [YLLs] and years lived with disability) by race/ethnicity using population-based cancer registry data collected in 2013, vital statistics, and literature reviews. RESULTS: A total of 9.8 million DALYs (91% YLLs) were lost to cancer. Half of DALYs were due to lung (24%), breast (10%), colorectal (9%), and pancreatic (6%) cancers. Age-standardized DALY rate (ASR) ratios of non-Hispanic blacks (NHBs) over non-Hispanic whites (NHWs) for "all cancers" were 1.3 (95% CI=1.2, 1.4) times higher in men and 1.2 (95% CI=1.2, 1.3) times higher in women (ASR in NHBs 4,003 per 100,000 in men and 3,329 in women vs 3,088 and 2,758 in NHWs, respectively); ASRs were also higher in NHB for 15 cancers. Compared with NHWs, Hispanics and non-Hispanic Asians exhibited lower ASR for "all cancers" and common cancers, contrasting with a higher ASR for infection-related cancers (stomach, liver, cervix). CONCLUSIONS: The cancer burden was highest in NHBs, followed by NHWs, Hispanics, and non-Hispanic Asians. In all races/ethnicities, the cancer burden was largely driven by YLLs, highlighting the need to prevent death at middle age through broad implementation of structural and behavioral measures of primary prevention, early detection, and treatment.

Disparities in melanoma incidence and mortality in South-Eastern Europe: Increasing incidence and divergent mortality patterns. Is progress around the corner?

INTRODUCTION: Most countries in South-Eastern Europe (SEE) have lower incidence, but higher mortality rates of malignant melanoma (MM) of the skin compared to North-Western Europe (NWE). We explored trends in MM incidence and mortality in SEE countries by sex and age and compared them with the trends in NWE. METHODS: We obtained data on incident cases and deaths from MM (ICD-10 code C43) from 11 population-based cancer registries in Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Malta, Romania, Serbia, Slovakia, Slovenia and Turkey. We calculated age-specific rates for 25-49 ('young'), 50-69 ('middle aged') and 70+ years ('older') and estimated the average annual percent of change in incidence and mortality trends 2000-2010 according to age group and sex, using joinpoint regression analysis. FINDINGS: The incidence rates of MM across the region were uniformly increasing. Significant increases in mortality rates were observed in middle aged men in Serbia and Bulgaria, middle aged women in Slovenia, older men in the Czech Republic, Serbia and Turkey, and older women in Slovenia and Serbia. INTERPRETATION: While MM incidence rates were still increasing across SEE, mortality trends diverged and were less favourable than in NWE. Empowering cancer registration and improving the quality of incidence and mortality data will be essential for monitoring progress in MM control. In the context of prevention of melanoma, disparities in early detection appear to be widening the gap between SEE and NWE, while the provision of care to patients with advanced disease is likely to prove a challenge for regional healthcare budgets.

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.

Impact of active surveillance, chlorambucil, and other therapy on health-related quality of life in patients with CLL/SLL in the Netherlands.

As survival of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) increases and the number of patients who live long rises, health-related quality of life (HRQoL) becomes a relevant endpoint. Few studies investigated this, mainly as a secondary endpoint in randomized clinical trials where patients with early stage CLL/SLL, and elderly/frail patients were underrepresented. The aim of our study was to assess HRQoL in a population-based setting, including these previously underrepresented patients. Out of 175 patients diagnosed with CLL/SLL between 2004 and 2011, 136 (78 %) returned the HRQoL questionnaire. The outcomes were compared to an age- and sex-matched norm population. Detailed data on stage and treatment were extracted from a population-based hematological registry (PHAROS). Patients ever treated for CLL/SLL reported significantly poorer HRQoL than the norm population (p < 0.01 with large clinically important differences. Interestingly, no differences were observed between the norm population and patients under active surveillance. In contrast to our hypothesis, patients treated with chlorambucil reported the lowest HRQoL scores. Drastic, long-lasting negative effects of starting treatment on HRQoL cannot be excluded, whereas active surveillance does not seem to provoke worrying, anxiety, or depressive symptoms. Further elaborate research into the impact of starting therapy on HRQoL is needed, especially in patients that are underrepresented in most clinical trials, and thoroughly consider its results during revision of treatment guidelines.

Sex differences in melanoma survival are not related to mitotic rate of the primary tumor.

PURPOSE: Based on prior studies, we concluded that the female advantage in melanoma survival is caused by biological factors and not by differences in patient behavior. In this study, we investigated whether this biological advantage was caused by more aggressive tumors in males, as measured by mitotic rate (MR). METHODS: Data for patients with complete information on MR, Breslow thickness, ulceration and primary tumor location were extracted from the database of Melanoma Institute Australia in Sydney. A negative binomial regression model was used to assess the independent predictive value of sex for MR. Also, the impact of MR on the sex survival advantage was investigated using Cox proportional hazards models. RESULTS: A total of 9,306 patients were included in the analysis. Although males had a slightly higher MR at diagnosis, sex was not an independent predictor of MR after adjustment for all other prognostic factors: incidence rate ratio 0.98, 95 % confidence interval (CI) 0.93-1.02, p = 0.32. After adjustment for all prognostic factors, females had a survival advantage of 36 % (hazard ratio 0.65, 95 % CI 0.55-0.75, p < 0.001). When added as a confounder, MR did not influence this sex hazard ratio. CONCLUSIONS: Sex did not independently predict the aggressiveness of a primary melanoma. Furthermore, MR did not influence the known female survival advantage. Based on these results, the biological trait underlying sex survival differences in melanoma seems not to be tumor-related and therefore is more likely to be caused by host factors.

Towards better implementation of cancer screening in Europe through improved monitoring and evaluation and greater engagement of cancer registries.

Proposals to improve implementation, monitoring and evaluation of breast, cervical and colorectal cancer screening programmes have been developed in a European project involving scientists and professionals experienced in cancer registration (EUROCOURSE). They call for a clear and more active role for cancer registries through better interfaces with cancer screening programmes and adapting data contents of cancer registries for evaluation purposes. Cancer registries are recognised as essential for adequate evaluation of cancer screening programmes, but they are not involved in screening evaluation in several European countries. This is a key barrier to improving the effectiveness of programmes across Europe. The variation in Europe in the implementation of cancer screening offers a unique opportunity to learn from best practices in collaboration between cancer registries and screening programmes. Population-based cancer registries have experience and tools in collecting and analysing relevant data, e.g. for diagnostic and therapeutic determinants of mortality. In order to accelerate improvements in cancer control we argue that cancer registries should take co-responsibility in promoting effective screening evaluation in Europe. Additional investments are vital to further development of infrastructures and activities for screening evaluation and monitoring in the national settings and also at the pan-European level. The EUROCOURSE project also aimed to harmonise implementation of the European quality assurance guidelines for cancer screening programmes across Europe through standardising routine data collection and analysis, and definitions for key performance indicators for screening registers. Data linkage between cancer and screening registers and other repositories of demographic data and cause of death and where available clinical registers is key to implementing the European screening standards and thereby reducing the burden of disease through early detection. Greater engagement of cancer registries in this collaborative effort is also essential to develop adequate evaluation of innovations in cancer prevention and care.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010.

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989-2010 and mantle cell lymphoma in the period 2001-2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989-1993 and the period 1994-1998 [5-year relative survival 42% (95%CI: 39%-45%) and 41% (38%-44%), respectively], but increased to 46% (43%-48%) in the period 1999-2004 and to 58% (56%-61%) in the period 2005-2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.

Recent trends in incidence of five common cancers in 26 European countries since 1988: Analysis of the European Cancer Observatory.

BACKGROUND: Individual country- and cancer site-specific studies suggest that the age-adjusted incidence of many common cancers has increased in European populations over the past two decades. To quantify the extent of these trends and the recent burden of cancer, here we present a comprehensive overview of trends in population-based incidence of the five common cancers across Europe derived from a new web-based portal of the European cancer registries. METHODS: Data on incidence for cancers of the colon and rectum, prostate, breast, corpus uteri and stomach diagnosed from 1988 to 2008 were obtained from the European Cancer Observatory for cancer registries from 26 countries. Annual age-standardised incidence rates and average annual percentage changes were calculated. RESULTS: Incidence of four common cancers in eastern and central European countries (prostate, postmenopausal breast, corpus uteri and colorectum) started to approach levels in northern and western Europe, where rates were already high in the past but levelled off in some countries in recent years. Decreases in stomach cancer incidence were seen in all countries. DISCUSSION: Increasing trends in incidence of the most common cancers, except stomach cancer, are bad news to public health but can largely be explained by well-known changes in society in the past decades. Thus, current and future efforts in primary cancer prevention should not only remain focussed on the further reduction of smoking but engage in the long-term efforts to retain healthy lifestyles, especially avoiding excess weight through balanced diets and regular physical exercise.

Power analysis to detect time trends on population-based cancer registries data: When size really matters.

Detecting statistically significant trends in incidence with cancer registries data not only depends on the size of their covered population but also on the levels of incidence rates, duration of diagnostic period and type of temporal variation. We simulated sample sizes of newly diagnosed cases based on a variety of plausible levels of cancer rates and scenarios of changing trends over a period of about 30 years. Each simulated set of cases was then analysed with joinpoint regression models. The power was derived as the relative frequency of the simulation runs where the p-value of the coefficient was less than 0.05 under the alternative model. In case of a decreasing trend with no change of direction (join), an Annual Percentage Change (APC) of 1% for an average rate of 10 per 100,000 is detectable in populations of half a million inhabitants or more with a nominal power of 80%. In a model with one joinpoint followed by an increasing trend, the minimum detectable APC increases, and an APC of about 2%, can be detected only with populations of at least 2 million. For analyses requiring a larger sample size than the actual covered population, alternative organisational strategies should be considered, such as an extension of population coverage or data pooling and merging from registries with comparable data. (i.e. when heterogeneity across merging registries is low or acceptable for the specific study question).