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BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

BACKGROUND REMERA (REgistre des Malformations En Rhone-Alpes) is a registry of congenital malformations that covers 58,000 births annually in Central-East France. In 2010, the registry raised an alarm to the health authorities (Sante publique France, SpF) about three cases of a unilateral isolated transverse upper limb reduction defect (UITULRD) in a small subarea; the general prevalence of this defect is one case in 10,000 births. In the following years, more infants were born with the same malformation in the same territory of the Ain department. Public health authorities, supported by an expert committee, rejected the existence of a cluster, but we aim here at providing evidence for this cluster. METHODS Geocoded data for all UITULRD cases (ICD-10 codes Q71.2 and Q71.3) were extracted from the REMERA database. We conducted a Kulldorff cluster analysis of these data, using the spatial SaTScanTM algorithm. RESULTS The analysis found a cluster of eight cases of UITULRD among the 8,204 births occurring between 2009 and 2014 within a circle of 16.24 km radius centered on a village of the Ain department, whereas 0.82 cases were expected under a uniform probability of such a birth throughout the registry territory. This represents an almost 10fold excess over the expected number of cases (p = .0057). CONCLUSIONS The arguments used to deny the cluster are disputed and we present the evidence supporting its reality. The controversy that has followed the alarm has compromised the search for the cause(s) of this excess of rare malformations.

Background Survival from metastatic cutaneous melanoma is substantially lower than for localized disease. Treatments for metastatic melanoma have been limited, but remarkable clinical improvements have been reported in clinical trials in the last decade. We described the characteristics of US patients diagnosed with cutaneous melanoma during 2001-2013 and assessed trends in short-term survival for distant-stage disease. Methods Trends in 1-year net survival were estimated using the Pohar Perme estimator, controlling for background mortality with life tables of all-cause mortality rates by county of residence, single year of age, sex, and race for each year 2001-2013. We fitted a flexible parametric survival model on the log-hazard scale to estimate the effect of race on the hazard of death because of melanoma and estimated 1-year net survival by race. Results Only 4.4% of the 425 915 melanomas were diagnosed at a distant stage, cases diagnosed at a distant stage are more commonly men, older patients, and African Americans. Age-standardized, 1-year net survival for distant-stage disease was stable at approximately 43% during 2001-2010. From 2010 onward, survival improved rapidly, reaching 58.9% (95% confidence interval = 56.6% to 61.2%) for patients diagnosed in 2013. Younger patients experienced the largest improvement. Survival for distant-stage disease increased in both Blacks and Whites but was consistently lower in Blacks. Conclusions One-year survival for distant-stage melanoma improved during 2001-2013, particularly in younger patients and those diagnosed since 2010. This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities exist between Blacks and Whites, suggesting differential access to treatment.

Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

Cancer incidence, survival and mortality are essential population-based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population-based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use.

The purpose of this article was to compare the performance of digital mammography using hardcopy image reading against film-screen mammography in a French national routine population-based screening program with a decentralized organization. The French context offered the opportunity to examine separately computed radiography and direct digital mammography performances in a large cohort.The study includes 23,423 direct digital mammography, 73,320 computed radiography, and 65,514 film-screen mammography examinations performed by 123 facilities in Bouches du Rhône, France, for women 50-74 years old between 2008 and 2010. We compared abnormal mammography findings rate, cancer detection rate, and tumor characteristics among the technologies.Abnormal finding rates were higher for direct digital mammography (7.78% vs 6.11% for film-screen mammography and 5.34% for computed radiography), particularly in younger women and in denser breasts. Cancer detection rates were also higher for direct digital mammography (0.71% vs 0.66% for film-screen mammography and 0.55% for computed radiography). The contrast between detection rates was stronger for ductal carcinoma in situ. Breast density was the main factor explaining the differences in detection rates. For direct digital mammography only, the detection rate was clearly higher in dense breasts whatever the age (odds ratio, 2.20). Except for grade, no differences were recorded concerning tumor characteristics in which the proportion of high-grade tumors was larger for direct digital mammography for invasive and in situ tumors.Direct digital mammography has a higher detection rate than film-screen mammography in dense breasts and for tumors of high grade. This latter association warrants further study to measure the impact of technology on efficacy of screening. The data indicate that computed radiography detects fewer tumors than film-screen mammography in most instances.

Background Wide geographic variations in survival for gastric cancer in Europe have been reported. The aim of this study was to analyse the effect of stage at diagnosis, treatment and cancer characteristics on long-term survival for gastric cancer in populations covered by cancer registries. Methods We analysed survival in 4620 cases of gastric cancer from 17 European population-based cancer registries from 8 countries. Univariate and multivariate regression of relative survival were performed. Results Five-year relative survival varied between 10.6% and 24.0%, while 10-year survival ranged from 7.7% to 23.0%. After adjustment for age and sex, the regional excess hazard ratio (EHR) of death was significantly higher in Ragusa, Granada, Yorkshire, Slovakia, Slovenia and Poland than in France, Northern Italy, The Netherlands and the Basque Country. After further adjustment for surgical resection versus no resection (a proxy of stage), the EHR of death remained significantly higher only in Granada and Yorkshire than in the reference country (France). After adjustment for stage, the EHR was significantly higher only in Yorkshire (EHR: 1.51; 95% confidence interval (CI): 1.29–1.77). The EHR in this area was limited to the first year following diagnosis. Conclusion Differences across Europe in gastric cancer survival depend to a large extent on differences in stage at diagnosis. However they do not explain all variations. Quality of management and treatment can explain some differences.

Objective To study the performance of a new method designed to measure discrepancy between real prescriptions and evidence-based reference treatments. Methods Two different indices (additive and multiplicative) are proposed to summarize deviation between prescription and reference. Deviations thought to be observed in a population of prescribers are simulated in diverse hypothetical situations in the presence or absence of evidence-based references. The performances of both indices are compared and their sensitivities to change are explored. Results Both indices are sensitive to variation in prescriber behaviour. The additive index allows a more accurate analysis of deviation while the multiplicative index is simpler to implement and interpret but more sensitive to change. Conclusion The two deviation indices may be used as new tools in surveys or trials dealing with prescribing practices.

Objective: To estimate risks for laryngeal/hypopharyngeal cancer associated with occupational titles and industrial activities. Methods: A multicentre population-based case-control study was conducted in the early 1980s in six southern European areas. Analyses included 1010 male cases and 2176 controls. Odds ratios (ORs) (adjusted for age, study area, tobacco consumption, and alcohol consumption) were estimated for 156 occupations and 70 industrial activities. Results: An excess risk has been confirmed for categories of construction workers, potters (OR: 5.91, 95% confidence intervals 1.46-24.0), butchers (2.53, 1.22-5.22), barbers (2.33, 1.00-5.40), laborers not otherwise specified (1.52, 1.12-2.06), as well as for men who had been employed in railway transport (1.52, 0.97-2.39), shipbuilding (2.05, 0.89-4.94), and hotels (2.06, 0.89-4.75). An association was also found for shoe finishers (3.23, 0.75-13.9), loggers (2.07, 0.87-4.90), and some groups of metal workers. ORs for loggers, butchers, railway transport workers, laborers, and reinforced concreters increased with duration of employment. The suggestion of a risk for machine operators among woodworkers (3.10, 0.92-10.5) conflicts with previous findings. No significant excess of risk was found for categories previously reported to be associated with laryngeal and hypopharyngeal cancer, such as drivers, mechanics, welders, machinists, and painters. Conclusions: The present study provides additional evidence to the hypothesis of a risk of cancer of the larynx/ hypopharynx for workers engaged in jobs in the construction, metal, textile, ceramic, and food industries and in railway transport. Loggers were also found at risk; a previously unreported finding.

Objective: To investigate the effect of exposure to occupational agents on the risk of hypopharyngeal/laryngeal cancer. Methods: Case-control study conducted during 1979–1982 in six centres in South Europe. An occupational history and information on exposure to non-occupational factors were collected for 1010 male cases of hypopharyngeal/laryngeal cancer as well as for 2176 population controls. The exposure to 10 occupational agents was assessed through a job-exposure matrix. As occupational histories had been collected since 1945 major analyses were restricted to subjects aged less than 55 years (315 cases and 819 controls). Results: Significant elevated risks adjusted for non-occupational variables (smoking, alcohol consumption and diet) and other occupational exposures were consistently found for organic solvents (odds ratio (OR) for ever-exposure: 1.7, 95% confidence interval: 1.1–2.5) and asbestos (OR: 1.6, 1.0–2.5). A significant positive trend for both probability of exposure and duration was found for exposure to solvents. A positive association between exposure to formaldehyde and laryngeal cancer was also suggested. No association was found for exposure to arsenic and compounds, chromium and compounds, and polycyclic aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7). Conclusions: In our study occupational exposure to solvents was associated with an increased risk of hypopharyngeal/laryngeal cancer. Results also provide additional evidence of an excess of risk for exposure to asbestos.

This article analyses time trends and geographical variations of thyroid cancer by histological type. Incidence data were provided by 8 French cancer registries over the period 1978–1997, with 3853 adult cases reported. To assess the effects of age, period, cohort and area on incidence, log-linear Poisson regression models were used. Thyroid cancer increased exponentially from the cohort born in 1925. This increase was essentially due to papillary cancer, which increased by 6.2% per year in men and 8.1% per year in women over the entire period (1978–1997). In women, the recent trends were significantly different between the studied geographical areas. The analysis shows that the increase in thyroid cancer, essentially of the papillary type, is not recent. It may be attributed to a possible screening effect or to an increase in the number of “incidentally” discovered cases linked to the use of modern diagnostic tools.

Epidemiological studies have shown a marked decline in gastric cancer incidence and opposite patterns between proximal and distal sites among different populations. Little is known about trends by histological type. The aim of this study was to analyse the change in gastric cancer incidence patterns by investigating the role of temporal components as determinants of such trends in the population of the Cote d'Or area (France) registered between 1976 and 1995. Gastric cancer incidence decreased over time. There was a decrease in incidence rates for distal cancers (-3.5% P < 0.001 per year in men and -4.6% P < 0.01 in women). In contrast, there was a non-significant increase of proximal cancer incidence in men and in women. Rates of adenocarcinomas decreased, whereas the incidence rates of undifferentiated carcinomas and of other histological types remained quite stable. There was a decrease in cumulative risk throughout the studied cohorts, whereas risk for proximal cancer remained stable and decreased slightly for distal localization. For adenocarcinomas, earlier birth cohorts showed a slight decrease in rates, whereas there was an increase for recent cohorts. Subsite and histological-specific analysis, in revealing different time trends in incidence, suggest, at least partly, different aetiologies for gastric cancer, and future aetiological studies must distinguish proximal and distal cancers.

The Cox model is widely used in the evaluation of prognostic factors in clinical research. In population-based studies, however, which assess long-term survival of unselected populations, relative survival models are often considered more appropriate. In both approaches, the validity of proportional hazard hypothesis should be evaluated. To explore the validity of the proportional hazard assumption in a population-based study of colon cancer, to propose non-proportional hazard relative survival models and to evaluate their utility. The use of a piecewise proportional hazard relative survival model in colon cancer has shown that the effects of most clinical prognostic factors such as age, period of diagnosis and stage are non-proportional. The non-proportional hazard relative survival models developed in this article have been found to be efficient tools for better understanding the time-dependent aspect of prognostic factors.

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII®) test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII®test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45–74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening. © 2001 Cancer Research Campaign http://www.bjcancer.com

The prognosis of Hodgkin's disease (HD) has improved during the last 30 years. This study was planned to analyse long-term survival of HD patients and to compare survival rates estimated from clinical trials and population-based data. Individual data were analysed on 2755 adult HD patients entering randomised clinical trials of the British National Lymphoma Investigation (BNLI) between 1970 and 1987, and 5064 patients with HD incident 1978–1984 recorded in the UK population-based cancer registries participating in the EUROCARE study. Relative survival of Hodgkin's disease patients allowing for mortality expected from general population rates was analysed by a proportional hazards regression model including covariates. Although relative mortality decreased with longer follow-up, it was still significantly positive at 9–10 years after diagnosis in both the clinical trials and the population-based data sets. Relative mortality was worse for late stage than for early stage patients even at 10–15 years after first treatment (BNLI data). Whereas 10-year relative survival was identical in trials and population-based patients at ages under 45 years (>69%), it was much higher in BNLI older patients than in the population-based patients. In the older age group (65–74 years) the BNLI patients had 39% relative survival whilst for the population-based patients it was only 27%. Generalisation of clinical trials results to the general population must be done with caution, especially for older patients.

In France, as in several other European countries, prevalence has to be estimated from the modelling of 2 of the 3 basic epidemiological measures of incidence, mortality, and survival. Since, in these countries, follow-up of cancer patients is only made in a few registries, we explored the feasibility of estimating prevalence in the absence of follow-up data. The method, which used only incidence and mortality, was validated on Danish data and applied to France. For this latter country, the estimation procedure is based on the recorded mortality data and an estimate of incidence for the entire country. It is applied to selected sites of cancer, which account for 80% of the estimated incidence. In 1992, the prevalence of patients who had such a diagnosis amounts to 538,000 women and 424, 000 men. The most frequent cancer sites are head and neck, breast, and large bowel. Most of the cancer sites present an increase in prevalence proportion between 1987 and 1992. The larger increases concern breast and prostate cancer.

Objective To evaluate the effectiveness of a mass screening programme for breast cancer in a French population where hormone replacement therapy (HRT) is common and where mammography is prescribed outside the programme for asymptomatic women. Methods From 1993 to 1996 inclusive, 41 062 women underwent a first test and 48 275 a second or third test in the Bouches du Rhône programme. Their HRT status was ascertained at the time of the test. False positive and false negative tests were identified at one year follow up. The incidence of interval cancers was estimated up to three years after the screening test. Results The odds of being detected at screening rather than as an interval cancer within one year of the test was five times greater among non-users of HRT than among users (odds ratio (OR) 5.14 (confidence interval 2.5 to 11.8)). This high reduction in sensitivity among users (71% v 92%) was associated with a very small reduction in specificity at the incident screen only. The incidence of interval cancers among HRT users was 3.5 times that of non-users within the first year after the test and 1.7 times during the following two years. Conclusions When the early results of a programme have been used to measure its effectiveness they should be reassessed in populations where HRT is in widespread use. As interval cancers had better prognostic factors in HRT users than in non-users, the efficacy of a screening programme in such populations should be the subject of further studies.

The EUROCARE Study is a European Union project to assemble survival data from population-based cancer registries and analyse them according to standard procedures. We investigated and compared liver, pancreatic and biliary tract cancer survival in 17 countries from 1985 to 1989. Time trends in survival over the 1978-1989 period were also investigated in 12 countries. The overall European mean 1 year relative survival was 16% for primary liver cancer, 26% for biliary tract cancer and 15% for pancreatic cancer. The corresponding 5-year relative survival was 5, 12 and 4%, respectively. Taking the European average as the reference, the relative risk (RR) of death was at least 20% higher for the three cancers in Denmark and Estonia. Survival tended to be higher in Spain for primary liver cancer and biliary tract cancer. Gender had little influence on survival whilst age at diagnosis was inversely related to prognosis. There was an improvement in 1-year relative survival rate for primary liver cancer: relative risk (RR) of 0.68 (95% confidence interval (CI) of 0.60-0.77) for 1987-1989 versus 1978-1980 and biliary tract cancer (RR 0.77, 95% CI 0.68-0.87). There was less variation in 5-year relative survival rate over time. Some intercountry survival differences for primary liver, biliary tract and pancreatic cancers exist over Europe. Differences in quality of care, in particular treatment aggressiveness, may explain some of these differences in survival. New approaches to the management of these cancers need to be found.

Objective To review the epidemiological evidence on neuroblastoma and to use it in the framework of a statistical model to assess the value of screening children for this disease at different ages. Procedure A simple two-stage model of the disease is used to estimate the prevalence at screening from incidence and from the distribution of the length of the preclinical phase. Results It is shown that screening at 6 months would anticipate the diagnosis for a maximum of 25 cases per million. Given the detection rate of the existing programs, it would imply a 50% overdiagnosis. Furthermore, if the case with an anticipated diagnosis had a survival rate of 85%, the reduction in mortality would be at most 20%, whatever the age at screening. To detect such a reduction would need several millions of children to be enrolled in a trial. Conclusions Considering these results and the likely persistence of overdiagnosis when screening at 12 months, the epidemiological and statistical evidence plead against further research on neuroblastoma screening. Its efficacy can be evaluated with sufficient reliability from the present evidence: the likely small benefit on mortality does not compensate for the cost of overdiagnosis. Med. Pediatr. Oncol. 31:401–407, 1998. © 1998 Wiley-Liss, Inc.

Breast cancer is the most frequent malignancy among women in developed countries. Prognosis is better than for other major cancers, and an improvement in survival has been reported for several populations in recent decades. Within the framework of EUROCARE, a population-based project concerned with the survival and care of cancer patients in Europe, we analysed data from 119,139 women diagnosed with breast cancer between 1978 and 1985 in 12 countries and followed for at least 6 years. Multiple regression models of relative survival, which take mortality from all other causes in each area into account, were used to estimate the effect of age, period of diagnosis and country on survival. For the comparison between countries, survival rates were age-standardised to the age structure of the entire study population. Women aged 40-49 years at diagnosis had the best prognosis in all countries and throughout the study period. Women younger than 30 years at diagnosis had a worse prognosis than those aged 30-39. The highest relative survival at 5 years was in Finland and Switzerland (about 74%), intermediate levels were found for Italy, France, The Netherlands, Denmark and Germany (about 70%) and the lowest rates were in Spain, the United Kingdom, Estonia and Poland (55-64%). During the 6 months following diagnosis, survival was highly dependent on age and was sharply lower in women older than 49 years. For women surviving more than 6 months after diagnosis, survival was similar for all ages, although women aged 40-49 still had the better prognosis. The average rate of death from breast cancer fell by about 2.5% for each year of diagnosis between 1978 and 1985. This improvement manifested mainly in younger and older women, for whom survival was initially less good. The largest improvement was seen in Poland (-15% death risk per year). We suggest that the better survival of women aged 40-49 at diagnosis is related to lower levels of circulating sex hormones, resulting in reduced stimulation of tumour cell growth. Early diagnosis may also be important in the peri-menopausal period due to increased diagnostic attention. Low survival in the United Kingdom may be due to inadequate adherence to consensus treatment guidelines and greater variation in treatment.

Summary Background Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries. Methods Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at routine health checks or during investigation of other disorders) and mortality rates were also compared. Findings Between 1987 and 1991, 1672 cases of neuroblastoma were diagnosed in children under 15 years old (France, 624; Austria, 69; Germany, 493; UK, 486). Age-standardised annual incidence was significantly lower in the UK (10.41/million) than in France (12·5) and Germany (11·4). In the UK a deficit of low-stage disease in infants was accompanied by an excess of stage IV in older children. The UK had significantly fewer incidental diagnoses (8%) than Austria (27%) and Germany (34%). UK mortality rates were significantly higher than German or French rates. Interpretation In the UK, neuroblastoma diagnosis is delayed, possibly because of a less rigorous system of health checks for children. Although some overdiagnosis occurs in mainland Europe, our data suggest that in the UK some low-stage cases, undetected in infancy, may later present as advanced disease. This finding has implications for screening programmes and organisation of routine surveillance of infant health in the UK.

The synergy between two risk factors measures the extent to which each of them is more harmful in combination with the other than when acting alone. Relative risk models which describe interaction between risk factors with a few parameters are well adapted to the quantification of synergy. A simple measure of synergy and a method for its estimation with the help of relative risk models are proposed. This concept of synergy provides a simple interpretation of the non-linear parameter of several classical relative risk models. The discussion is illustrated with examples taken from cancer epidemiology of the upper aerodigestive tract.

The proliferative potential of central neurocytomas was determined in a biopsy series of 36 cases and compared with clinical outcome. The mean size of the growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first biopsy, was 2.8 +/- 2.5 with a range of 0.1 to 8.6%. Neurocytomas with an MIB-1 LI > 2% comprised 39% of cases and showed a close correlation with the presence of vascular proliferation (p = 0.0006). The Kaplan-Meier analysis showed a highly significant difference in disease-free survival between the 2 groups (p = 0.0068). Over an observation time of 150 months, there was a 22% relapse among patients with an MIB-1 LI less than 2% and a 63% chance of relapse among those with an MIB-1 LI greater than 2%. We propose the term "atypical central neurocytoma" for the latter subset, corresponding to WHO grade II.

A pilot study of neuroblastoma mass screening was initiated in January 1990 in the Rhone French district. The expected number of births per year is 26,000. The study is designed for a 5-year period with three major goals: 1) measurement of the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the technical value of high-pressure liquid chromatography (HPLC) as a screening method; and 3) detailed biological characterization of all detected tumors. 61,551 children were screened between May 1, 1990 and December 31, 1993. Participation was 69% in 1990, 81.5% in 1991, and over 83% in 1992. HPLC was a satisfactory assay method. The number of clinical examinations required for positive tests as defined in the protocol is 1 per 3,621 tests. The false positive rate is 1 per 3,583 tests. Eight neuroblastomas were discovered by-screening (one stage I, three stage II, one stage III, three stage IVs). All are alive and well but were good prognosis cases according to the main prognostic factors. Five patients were discovered before screening (so called Halo effect): one stage I, one stage III, three stage IVs. One died of disease and four are alive in complete remission after treatment. Two patients were false negative (one stage III with N-myc amplification, one stage IV with bad prognosis features) and three cases of neuroblastoma were missed because of noncompliance with the screening program. This pilot study concludes on the feasibility of a mass screening program in France. The estimated cumulative incidence of neuroblastoma at 3 years is 1 per 4,375 living births and overdiagnosis is probable. All the detected cases were of good prognosis and the false negative ones were poor prognosis cases.

Cancer incidence, survival and mortality are essential population-based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population-based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use.

Introduction: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990–1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhone district (1.5 M inhabitants, 26 000 births per year). Methods: Vanillyknandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffe's kinetic method on Technicon RA-XT(™). VMA and HVA were expressed as μg/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. Results and discussion: The overall participation rate for the 5-year period was 82.2%. Out of 105 293 infants tested from 128 126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastoma as it is presently being followed up.

Summary Background: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. Aim of the review: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of upmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. Conclusion: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.

The main causes of cancer of the larynx and hypopharynx are smoking cigarettes and drinking alcohol. However, for these as well as for other cancers of the upper aerodigestive tract, some dietary components, mainly low consumption of fruit and vegetables, have been observed to be associated with increased cancer risk. We report results from a multicenter case-control study carried out in six regions of Europe located in northern Spain, northern Italy, Switzerland, and France. A total of 1,147 males with cancer (cases) and 3,057 population controls were interviewed on usual diet, lifelong drinking and smoking habits, and occupational history. Cancer cases had histologically verified epidermoid carcinomas. The cancers were classified in two anatomic sub-entities: the epilarynx (hypopharynx and upper part of the larynx), which enters into contact with the bolus and the air; and the endolarynx, through which air and tobacco smoke pass, but not the bolus. A previous report from this study found that alcohol drinking presents a greater risk factor for cancer of the epilarynx than for cancer of the endolarynx. The main results regarding diet indicate that high intake of fruit, vegetables, vegetable oil, fish, and low intake of butter and preserved meats were associated with reduced risk of both epilaryngeal and endolaryngeal cancers, after adjustment for alcohol, tobacco, socioeconomic status, and non-alcohol energy intake. Among nutrients, a reduced risk was found for high intake of vitamins C and E and for a high polyunsaturated/saturated fatty acids (P/S) ratio. While these variables are relevant in scoring nutritional behaviour, it remains unresolved whether the biologic properties of these nutrients play a role in the apparent protective effect.

The main etiologic factors of cancers of the larynx and hypopharynx are alcohol and tobacco, and their prevalence in different populations explains, to a large extent, the wide variations in incidence observed around the world. Besides these two main risk factors, however, diet also seems to play a role in determining the risk of these cancers. There is consistent evidence that low consumption of fruit and vegetables is associated with higher risk, after statistical adjustment for alcohol and tobacco. Consumption of vegetable oils and fish and a moderately high polyunsaturated/saturated fatty acid ratio (P/S ratio) were reported to be associated with reduced risk. Low intake of vitamin C, beta-carotene and vitamin E were reported consistently to be associated with higher laryngeal cancer risk, but there was no clear evidence that these micronutrients are better predictors of cancer risk than the principal food groups from which their intake levels were estimated, i.e., fruits, vegetables, vegetable oils, and fish. Given the overwhelming role of tobacco and alcohol in the etiology of these cancers and the extremely low incidence among nonsmokers/nondrinkers, the available studies provide no estimate of the role of diet in subjects not exposed to these factors. The evidence indicates, however, that, in the presence of tobacco and/or alcohol, low intake of fruit and vegetables may account for 25 to 50 percent of the cases among men.

The association between the consumption of preserved foods in infancy, childhood and adulthood and the risk of nasopharyngeal carcinoma was investigated in a case-control study among Singapore Chinese: 200 cases (73% male) were compared with 406 hospital controls (71% male). Significantly increased risks were observed in association with frequent adult consumption of salted soy beans (OR 7.3 for consumption 4 or more times per week, compared with never), canned pickled vegetables (p = 0.01; OR 4.5 for 4 or more times per week), "sze chuan chye", a salted Chinese tuber, (OR 2.4 for 4 or more times per month) and "kiam chye", salted mustard greens (OR 2.7 for 4 or more times per week). A protective effect of high vitamin-E intake in adulthood was observed (OR 0.5 for the highest third of the control range, as compared with the lowest).

The validity and precision of questionnaire assessments of the habitual intake of individuals are usually evaluated by comparison with reference measurements that are supposed to provide a best possible substitute for the individuals' true intake values. In the present paper, a measurement error model is presented, defining different types of error--random or systematic, and within or between individuals--that may occur in dietary intake measurements. It is then discussed how simple latent variable models (structural equation models) can be used to estimate the average magnitude of these various types of error. So far, approaches described for the analysis of dietary validity studies have all been based on the assumption that the random errors of repeat reference measurements, taken by the same method on different occasions, are uncorrelated, so that the average of a sufficiently large number of repeat reference measurements will provide an accurate ranking of individuals by true intake level. In the present paper it is described how, by additional comparison with a third type of measurement such as a biochemical marker, the validity of dietary questionnaire measurements can be evaluated even in situations where the random errors of repeat reference measurements can no longer be assumed to be independent.

Estimation of relative survival has become the first and the most basic step when reporting cancer survival statistics. Standard estimators are in routine use by all cancer registries. However, it has been recently noted that these estimators do not provide information on cancer mortality that is independent of the national general population mortality. Thus they are not suitable for comparison between countries. Furthermore, the commonly used interpretation of the relative survival curve is vague and misleading. The present article attempts to remedy these basic problems. The population quantities of the traditional estimators are carefully described and their interpretation discussed. We then propose a new estimator of net survival probability that enables the desired comparability between countries. The new estimator requires no modeling and is accompanied with a straightforward variance estimate. The methods are described on real as well as simulated data.

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

Time trends in cancer risk have often been summarised by the observation that mortality from cancers associated with tobacco is increasing rapidly, while mortality from all other cancers is either stable or falling slightly, this slight decline being dominated by the decrease in mortality from stomach cancer. Until recently, and with some variation between the sexes, this simple summary of cancer mortality trends would have been broadly correct for a number of developed countries, and it remains useful in dismissing claims of an impending and unexplained epidemic of cancer, but it does not apply to all countries, and in some there have recently been striking changes in the trends in mortality from cancers associated with tobacco. Cancer mortality has been widely accepted as the most important measure of progress against cancer, since it reflects the impact of cancer on people, and has been considered less subject to distortion than incidence or survival, although this is open to question. Cancer mortality also reflects trends in incidence and survival to a greater or lesser extent. There has been controversy, however, over how cancer mortality trends should be interpreted, as well as over which measures should be used to assess progress in cancer control. An overall summary of trends in mortality from all cancers combined is of limited value in assessing progress against cancer, in any case. Increases in a common lethal cancer may numerically dominate overall mortality trends, perhaps concealing declines in less common or less lethal cancers, while opposite trends in cancers of the lung and stomach, for example, might lead to an overall impression that little has changed. Further, up to a third of cancer patients will not die of cancer, and cancer mortality statistics do not reflect their experience at all. Cancer mortality trends only indirectly reflect trends in the number of people who are diagnosed with cancer in a given year, and those who do die of cancer in a given year may have been diagnosed more than 3 years previously, even though many die earlier: this blurs the responsiveness of routine cancer mortality statistics as a measure of recent progress, and alternative measures have been proposed. Trends in competing risks of death, especially at higher ages, may also complicate the interpretation of cancer mortality trends. The chance of developing cancer, and in that event, the chances of surviving it, are of direct interest to individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

BACKGROUND: Little information is available on the conditional probabilities of death among patients who survive for >5 years after a diagnosis with cancer. The objective of this study was to estimate the conditional probabilities of death for breast cancer, prostate cancer, colorectal cancer, and lung cancer in France. METHODS: The study included data from the French Network of Cancer Registries from 205,562 patients aged 4% at 10 years. During the 3 years after diagnosis, the probability of death was greater for older patients with breast cancer; then, it decreased less for younger patients compared with older patients, leading to a greater conditional probability of death among younger patients at 4 years and up to 10 years. The annual probability of death in patients with lung cancer decreased for both sexes but remained substantially higher for men than for women, reaching approximately 8% and 5%, respectively, at 10 years. CONCLUSIONS: Further studies would facilitate a better understanding of the observed differences in relative survival within European countries. Cancer 2009. © 2009 American Cancer Society.

Most of the information currently available on radiation effects comes from the observation of individuals who received high doses, either from one acute exposure or a series of exposures. Because of the uncertainties in extrapolating risks from these studies to the exposure circumstances of most cancers today (in particular, low-level environmental exposure), direct epidemiologic studies of populations receiving low doses chronically are needed. The effects which we want to quantify are likely to be small, however, and extreme care must therefore be put into the design of such studies if they are to be informative for risk assessment purposes. The areas of particular importance in designing risk assessment studies are reviewed. The advantages and limitations of various epidemiological study designs, and the problems and importance of dosimetry are discussed. Examples from the recent epidemiological literature are presented to illustrate the discussion.

Survival has risen steadily since the 1970s for most cancers in adults in England and Wales, but persistent inequalities exist between those living in affluent and deprived areas. These differences are not seen for children. For many of the common adult cancers, these inequalities in survival (the ‘deprivation gap') became more marked in the 1990s. This volume presents extended analyses of survival for adults diagnosed during the 14 years 1986–1999 and followed up to 2001, including trends in overall survival in England and Wales and trends in the deprivation gap in survival. The analyses include individual tumour data for 2.2 million cancer patients. This article outlines the structure of the supplement – an article for each of the 20 most common cancers in adults, followed by an expert commentary from one of the leading UK clinicians specialising in malignancies of that organ or system. The available data, quality control and methods of analysis are described here, rather than repeated in each of the 20 articles. We open the discussion between clinicians and epidemiologists on how to interpret the observed trends and inequalities in cancer survival, and we highlight some of the most important contrasts in these very different points of view. Survival improved substantially for adult cancer patients in England and Wales up to the end of the 20th century. Although socioeconomic inequalities in survival are remarkably persistent, the overall patterns suggest that these inequalities are largely avoidable.

The influence of hepatitis B virus infection, alcohol consumption, tobacco smoking and use of oral contraceptives on the risk of hepatocellular carcinoma (HCC) was evaluated in a hospital-based case-control study in Catalonia, in the Mediterranean coastal area of north-eastern Spain. A total of 96 HCC cases (86.5% of them with associated liver cirrhosis) and 190 age- and sex-matched controls were studied. The odds ratio of HCC and 95% confidence interval among hepatitis B surface antigen (HBsAg) carriers was 4.9 (1.3-21.9). The OR was not significantly elevated in smokers, and a marginally significant increased risk was found among users of oral contraceptives based on 6 female cases. There was a significant dose-response relationship between alcohol consumption and risk of HCC (chi 2 for trend: 24.3, p less than 0.001). Although hepatitis B infection was strongly associated with HCC, alcohol abuse leading to cirrhosis appears to be one of the main causes of HCC in this region.

The methods of calculation of survival corrected for independent cause of death are discussed, and a maximum likelihood method is proposed and illustrated by survival of colon cancer patients in Geneva. The methods which are at present favoured for doing such calculations are subject to various biases when estimating net survival if the populations are heterogeneous for life expectancy. The proposed maximum likelihood approach would eliminate these biases by enabling relevant adjustment for covariates which influence survival. The routine use of such methods would permit better comparison of survival within and between populations.

To study the performance of a new method designed to measure discrepancy between real prescriptions and evidence-based reference treatments.Two different indices (additive and multiplicative) are proposed to summarize deviation between prescription and reference. Deviations thought to be observed in a population of prescribers are simulated in diverse hypothetical situations in the presence or absence of evidence-based references. The performances of both indices are compared and their sensitivities to change are explored.Both indices are sensitive to variation in prescriber behaviour. The additive index allows a more accurate analysis of deviation while the multiplicative index is simpler to implement and interpret but more sensitive to change.The two deviation indices may be used as new tools in surveys or trials dealing with prescribing practices.

International audience; We present the main results of the first population-based cancers survival study gathering all French registry data. Survival data on 205,562 cancer cases diagnosed between 01/01/1989 and 31/12/1997 were analysed. Relative survival was estimated using an excess rate model. The evolution of the excess mortality rate over the follow-up period was graphed. The analysis emphasised the effect of age at diagnosis and its variation with time after diagnosis. For breast and prostate cancers, the age-standardised five-year relative survivals were 84% and 77%, respectively. The corresponding results in men and women were 56% versus 58% for colorectal cancer and 12% versus 16% for lung cancer. For some cancer sites, the excess mortality rate decreased to low values by five years after diagnosis. For most cancer sites, age at diagnosis was a negative prognostic factor but this effect was often limited to the first year after diagnosis.

Definition dans les differentes classifications La localisation ≪ tous cancers ≫ recouvre l’ensemble des cancers y compris les hemopathies, tous les codes topographiques de C00.0 a C80.9 de morphologie invasive; mais sont exclus les cancers de la peau autres que les melanomes, ce qui correspond en : CIM-O-2 :exclusion des localisations C44.0 a C44.9 si la morphologie est differente de M8720 a M8790 CIM-O-1:exclusion des localisations 173.0 a 173.9 si la morphologie est differente de M8720 a M8790 CIM-10 :exclusion des localisations C44.0 a C44.9

Une description de la base de donnees est presentee dans le chapitre suivant. Elle comprend notamment les elements concernant les effectifs analyses et l’etat de la base touchant la connaissance du statut vital. Le chapitre « Estimation de la survie par cancer » comprend l’ensemble des resultats de l’analyse de survie. Apres un rappel sur l’incidence et la mortalite du cancer (ou les taux sont rapportes pour 100 000 personnes-annees), la presentation type pour chaque site est la suivante.

L’ensemble de la methode est rapporte en detail dans l’article de Remontet et al (1). Nous en presentons ici les lignes principales.