Survival of European patients diagnosed with myeloid malignancies: a HAEMACARE study.

Population-based information on the survival of patients with myeloid malignancies is rare mainly because some entities were not recognized as malignant until the publication of the third revision of the International Classification of Diseases for Oncology and World Health Organization classification in 2000. In this study we report the survival of patients with myeloid malignancies, classified by updated criteria, in Europe. We analyzed 58,800 cases incident between 1995 to 2002 in 48 population-based cancer registries from 20 European countries, classified into HAEMACARE myeloid malignancy groupings. The period approach was used to estimate 5-year relative survival in 2000-2002. The relative overall survival rate was 37%, but varied significantly between the major groups: being 17% for acute myeloid leukemia, 20% for myelodysplastic/myeloproliferative neoplasms, 31% for myelodysplastic syndromes and 63% for myeloproliferative neoplasms. Survival of patients with individual disease entities ranged from 90% for those with essential thrombocythemia to 4% for those with acute myeloid leukemia with multilineage dysplasia. Regional European variations in survival were conspicuous for myeloproliferative neoplasms, with survival rates being lowest in Eastern Europe. This is the first paper to present large-scale, European survival data for patients with myeloid malignancies using prognosis-based groupings of entities defined by the third revision of the International Classification of Diseases for Oncology/World Health Organization classifications. Poor survival in some parts of Europe, particularly for treatable diseases such as chronic myeloid leukemia, is of concern for hematologists and public health authorities.

Pesticide exposure in farming and forestry and the risk of uveal melanoma.

PURPOSE: Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. METHODS: Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. RESULTS: 293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color. CONCLUSIONS: Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.

Occupational exposure to endocrine-disrupting chemicals and the risk of uveal melanoma.

OBJECTIVES: We investigated the association between occupational exposure to endocrine-disrupting chemicals (EDC) and the risk of uveal melanoma using international data of a case-control study from nine European countries. METHODS: After exclusion of proxy interviews, 280 cases and 3084 control subjects were included in the final analysis. Information on possible exposure to EDC was derived from 27 job-specific questionnaires (JSQ), which solicited detailed questions on occupational tasks. Relative risk estimates were based on the JSQ and potential exposure to a group of endocrine-disrupting agents. We constructed several exposure scores, taking into account intensity of exposure, use of personal protective equipment, and exposure duration. We calculated unconditional logistic regression analyses, adjusting for country, age, sex, eye color and a history of ocular damage due to intense ultraviolet (UV) exposure. RESULTS: The overall exposure prevalence to EDC was low reaching a maximum of 11% for heavy metals with endocrine-disrupting properties. Although working in some industries was associated with increased melanoma risk [such as dry cleaning: odds ratio (OR) 6.15, 95% confidence interval (95% CI) 2.0-18.96 and working in the glass manufacturing industry: OR 3.49, 95% CI 1.10-11.10], agent-specific risks were not elevated. The strongest possible risk increase was observed for organic solvents with endocrine-disrupting properties (OR 1.31, 95% CI 0.78-2.21). Calculation of exposure scores did not indicate consistently elevated results with higher score values. Sensitivity analyses did not alter these results. CONCLUSION: Occupational exposure to EDC was not associated with an increased risk for uveal melanoma.

Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma.

OBJECTIVES: The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries. METHODS: Incident cases of uveal melanoma and population as well as hospital controls were included and frequency matched by country, 5-year birth cohort and sex. Subjects were asked whether they had worked close to high-voltage electrical transmission installations, computer screens and various electrical machines, or in complex electrical environments. Measurements of two Scandinavian job-exposure matrices were applied to estimate lifelong cumulative EMF exposure. Unconditional logistic regression analyses, stratified by sex and eye colour were calculated, adjusting for several potential confounders. RESULTS: 293 patients with uveal melanoma and 3198 control subjects were interviewed. Women exposed to electrical transmission installations showed elevated risks (OR 5.81, 95% CI 1.72 to 19.66). Positive associations with exposure to control rooms were seen among men and women, but most risk increases were restricted to subjects with dark iris colour. Application of published EMF measurements revealed stronger risk increases among women compared to men. Again, elevated risks were restricted to subjects with dark eye colour. CONCLUSION: Although based on a low prevalence of exposure to potential occupational sources of EMF, our data indicate that exposed dark-eyed women may be at particular risk for uveal melanoma.

Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project.

Changing definitions and classifications of hematologic malignancies (HMs) complicate incidence comparisons. HAEMACARE classified HMs into groupings consistent with the latest World Health Organization classification and useful for epidemiologic and public health purposes. We present crude, age-specific and age-standardized incidence rates for European HMs according to these groupings, estimated from 66,371 lymphoid malignancies (LMs) and 21,796 myeloid malignancies (MMs) registered in 2000-2002 by 44 European cancer registries, grouped into 5 regions. Age-standardized incidence rates were 24.5 (per 100,000) for LMs and 7.55 for MMs. The commonest LMs were plasma cell neoplasms (4.62), small B-cell lymphocytic lymphoma/chronic lymphatic leukemia (3.79), diffuse B-cell lymphoma (3.13), and Hodgkin lymphoma (2.41). The commonest MMs were acute myeloid leukemia (2.96), other myeloproliferative neoplasms (1.76), and myelodysplastic syndrome (1.24). Unknown morphology LMs were commonest in Northern Europe (7.53); unknown morphology MMs were commonest in Southern Europe (0.73). Overall incidence was lowest in Eastern Europe and lower in women than in men. For most LMs, incidence was highest in Southern Europe; for MMs incidence was highest in the United Kingdom and Ireland. Differences in diagnostic and registration criteria are an important cause of incidence variation; however, different distribution of HM risk factors also contributes. The quality of population-based HM data needs further improvement.

Hormonal exposures and the risk of uveal melanoma.

OBJECTIVES: Several studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma. Therefore, the association between the risk of uveal melanoma and exposure to hormonal exposures was investigated in a case-control study from nine European countries. METHODS: Incident cases of uveal melanoma were frequency-matched to population and hospital controls by country, age, and sex. Female subjects were asked about their reproductive history, use of menopausal hormone replacement therapy and oral contraceptives. Among men, occupational handling of oils while working with transformers or capacitors which contain polychlorinated biphenyls (PCB) was solicited. Unconditional logistic regression analyses were calculated, adjusting for several potential confounders. Analyses were stratified by sex. RESULTS: Two hundred and ninety-three cases (165 men, 128 women) and 3,198 control subjects (2,121 men, 1,077 women) were interviewed. Among women, no associations were observed with hormonal status variables, intake of hormonal therapy or intake of oral contraceptives. Men showed an increased risk with occupational exposure to transformer/capacitor oils (OR = 2.74; Bonferroni-corrected 99.3% CI 1.07-7.02). However, these results were based on few exposed subjects only. CONCLUSION: The results of this study do not support the hypothesis of a hormonal influence in the carcinogenesis of uveal melanoma. Our finding of a potentially increased risk with PCB-containing oils requires further research.

Access to specialized pediatric cancer care in Switzerland.

BACKGROUND: Specialized pediatric cancer centers (PCCs) are thought to be essential to obtain state-of-the-art care for children and adolescents. We determined the proportion of childhood cancer patients not treated in a PCC, and described their characteristics and place of treatment. PROCEDURE: The Swiss Childhood Cancer Registry (SCCR) registers all children treated in Swiss PCCs. The regional cancer registries (covering 14/26 cantons) register all cancer patients of a region. The children of the SCCR with data from 7 regions (11 cantons) were compared, using specialized software for record linkage. All children <16 years of age at diagnosis with primary malignant tumors, diagnosed between 1990 and 2004, and living in one of these regions were included in the analysis. RESULTS: 22.1% (238/1,077) of patients recorded in regional registries were not registered in the SCCR. Of these, 15.7% (169/1,077) had never been in a PCC while 6.4% (69/1,077) had been in a PCC but were not registered in the SCCR, due to incomplete data flow. In all diagnostic groups and in all age groups, a certain proportion of children was treated outside a PCC, but this proportion was largest in children suffering from malignant bone tumors/soft tissue sarcomas and from malignant epithelial neoplasms, and in older children. The proportion of patients treated in a PCC increased over the study period (P < 0.0001). CONCLUSIONS: One in six childhood cancer patients in Switzerland was not treated in a PCC. Whether these patients have different treatment outcomes remained unclear.

Lymph node ratio as an alternative to pN staging in node-positive breast cancer.

PURPOSE: In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. PATIENTS AND METHODS: From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. RESULTS: Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION: LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.

Survival in patients with uveal melanoma in Europe.

OBJECTIVE: To estimate survival in patients in whom uveal melanoma was diagnosed between January 1, 1983, and December 31, 1994, in Europe. METHODS: Survival analysis of data from 32 cancer registries in 16 European countries adhering to the European Cancer Registry for 5788 patients with uveal melanoma diagnosed between January 1, 1983, and December 31, 1994, with follow-up to 1999. RESULTS: Five-year relative survival was 68.9% overall and remained stable with the period of diagnosis. Relative excess risk of death was 2.45 (95% confidence interval [CI], 2.10-2.86) in patients aged 75 years or older compared with patients aged 54 years or younger and was slightly higher in male patients (relative excess risk, 1.10; 95% CI, 1.02-1.19) than in female patients. Survival was similar in Nordic countries (relative excess risk, 1.03; 95% CI, 0.87-1.21) compared with the United Kingdom (reference country) and was lower in eastern and western European countries (1.26; 1.05-1.52, and 1.25; 0.90-1.60, respectively) compared with the reference country. CONCLUSIONS: In this large series of patients with uveal melanoma, 5-year relative survival remained stable with the introduction of conservative treatment in individuals in whom uveal melanoma was diagnosed between 1983 and 1994. We found differences in survival between sexes and in European areas that should be investigated in studies that consider tumor characteristics at the individual level.

Cancer survival in five continents: a worldwide population-based study (CONCORD).

BACKGROUND: Cancer survival varies widely between countries. The CONCORD study provides survival estimates for 1.9 million adults (aged 15-99 years) diagnosed with a first, primary, invasive cancer of the breast (women), colon, rectum, or prostate during 1990-94 and followed up to 1999, by use of individual tumour records from 101 population-based cancer registries in 31 countries on five continents. This is, to our knowledge, the first worldwide analysis of cancer survival, with standard quality-control procedures and identical analytic methods for all datasets. METHODS: To compensate for wide international differences in general population (background) mortality by age, sex, country, region, calendar period, and (in the USA) ethnic origin, we estimated relative survival, the ratio of survival noted in the patients with cancer, and the survival that would have been expected had they been subject only to the background mortality rates. 2800 life tables were constructed. Survival estimates were also adjusted for differences in the age structure of populations of patients with cancer. FINDINGS: Global variation in cancer survival was very wide. 5-year relative survival for breast, colorectal, and prostate cancer was generally higher in North America, Australia, Japan, and northern, western, and southern Europe, and lower in Algeria, Brazil, and eastern Europe. CONCORD has provided the first opportunity to estimate cancer survival in 11 states in USA covered by the National Program of Cancer Registries (NPCR), and the study covers 42% of the US population, four-fold more than previously available. Cancer survival in black men and women was systematically and substantially lower than in white men and women in all 16 states and six metropolitan areas included. Relative survival for all ethnicities combined was 2-4% lower in states covered by NPCR than in areas covered by the Surveillance Epidemiology and End Results (SEER) Program. Age-standardised relative survival by use of the appropriate race-specific and state-specific life tables was up to 2% lower for breast cancer and up to 5% lower for prostate cancer than with the census-derived national life tables used by the SEER Program. These differences in population coverage and analytical method have both contributed to the survival deficit noted between Europe and the USA, from which only SEER data have been available until now. INTERPRETATION: Until now, direct comparisons of cancer survival between high-income and low-income countries have not generally been available. The information provided here might therefore be a useful stimulus for change. The findings should eventually facilitate joint assessment of international trends in incidence, survival, and mortality as indicators of cancer control.

Incidence of uveal melanoma in Europe.

PURPOSE: To estimate incidence rates of uveal melanoma in Europe from 1983 to 1994. DESIGN: Incidence analysis of data from cancer registries adhering to the European Cancer Registry-based study on survival and care of cancer patients (EUROCARE) (cases diagnosed from 1983 to 1994). PARTICIPANTS: Data of 6673 patients with ocular melanoma (as defined by International Classification of Diseases for Oncology morphology codes 8720 to 8780 [melanoma] and International Classification of Diseases 9 (ICD9) codes 190.0 [iris and ciliary body], 190.5 [retina], 190.6 [choroid], and 190.9 [unspecified ocular location]) from 33 cancer registries of 16 European countries. METHODS: Incidence rate ratios (IRRs) were obtained from a multilevel Poisson regression model. MAIN OUTCOME MEASURES: Incidence rates and IRRs associated with demographic and geographic variables. RESULTS: Standardized incidence rates increased from south to north across registries, from a minimum of <2 per million in registries of Spain and southern Italy up to >8 per million in Norway and Denmark. The inclusion of tumors with unspecified ocular location (code 190.9) increased incidence rates in most United Kingdom registries, but not in the other geographic areas, where this code was seldom used for uveal melanomas. Incidence increased noticeably up to age 55 (IRR, 1.46 per 5 years; 95% confidence interval [CI], 1.36-1.57) but leveled off after age 75 (IRR, 0.99 per 5 years; 95% CI, 0.93-1.05), with intermediate levels midway (IRR, 1.18 per 5 years; 95% CI, 1.12-1.23). It was also higher in males (IRR, 1.22; 95% CI, 1.16-1.28). Rates were stable during the study period, but a cohort effect was evidenced, accounting for higher incidence rates in people born during the period 1910 to 1935 (P = 0.005). Incidence increased with latitude (P = 0.008), which explained most differences in rates among areas. CONCLUSIONS: In this large series of uveal melanomas, we found stable incidence during the years 1983 to 1994. The north-to-south decreasing gradient supports the protective role of ocular pigmentation. European ophthalmologists should develop guidelines to standardize the coding of tumors treated conservatively using the ICD classification to improve the registration and surveillance of uveal melanoma by cancer registries.

Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study.

Effective treatments for testicular cancer have been available since the 1970s, yet EUROCARE uncovered marked inter-country survival differences for this disease. To investigate these differences, we reviewed clinical records of 1350 testicular cancer cases diagnosed during 1987-1992 from 13 population-based cancer registries in nine European countries. Patients were followed up for life status and relapse. Ten-year observed survival was estimated by the Kaplan-Meier method. Cox multivariable analyses were performed separately for seminomas and non-seminomas. Overall, 66% of seminomas and 36% of non-seminomas were limited to the testis. Ten-year survival was 63% (Estonia) to 94% (Switzerland, Slovenia) for seminoma; 47% (Estonia) to 90% (Yorkshire, UK, The Netherlands) for non-seminoma. Multivariable analysis adjusted for country, age and stage showed that hazard ratios (HRs) of death differed little between western European registries, and were mainly attributable to differing stage at diagnosis. Significantly higher than reference HRs in Estonia and Poland suggest inadequacy or unavailability of treatments.

A modification to the flow method to estimate completeness in cancer registries with delayed registration.

OBJECTIVE: For registries that routinely delay case registration, the flow method does not accurately describe their completeness over time. A modification to allow for such a delay is proposed and tested. METHODS: Using original data set from Ticino Cancer Registry, Switzerland, a new data set (the delayed data set) was created by adding two years to the date of registration for each case in the original data set, to emulate the situation in a registry where registration is delayed by two years. Both the original and modified methods were then applied to both the original and the delayed data set. RESULTS: When applied to the delayed data, the original method produced estimates of completeness of 32 and 43% at one and two years after diagnosis. When the modified method was applied to the delayed data, the completeness at one and two years was correctly estimated at 0%. After the initial two-year time lag, completeness was consistently estimated by both methods. When applied to the original data, the modified method produced the same results as the original method. CONCLUSIONS: The proposed modification allows the method to be applied even when registration is delayed long after diagnosis-thus extending the range of registries for which the flow method can be used.

Unexpected additional increase in the incidence of thyroid cancer among a recent birth cohort in Switzerland.

Data collected by the Swiss Cancer Registries Network (ASRT/VSKR) have been used to analyse trends in thyroid cancer during the last available 20 years, to make within-country geographical comparisons for current incidence rates. Age-standardized (European population) incidence rates per 100,000 for all morphologies combined ranges from 1.62 to 2.99 among males and from 2.13 to 8.09 among females in Switzerland. Regression analyses for both sexes combined detected an increase in time for papillary cases and a decrease for other types. Age-period-cohort analyses revealed that the youngest cohorts of men and women born after 1940 had an increased risk of all types of thyroid cancer while the cohort of people born between 1920 and 1939 were at increased risk of the papillary subtype. Assuming a higher sensitivity to ionizing radiation among the youngest people, a Chernobyl effect cannot be definitively excluded and continuous study of this topic should be encouraged.

Survival from rare cancer in adults: a population-based study.

BACKGROUND: Rare cancers are a challenge to clinical practice, and treatment experience, even in major cancer centres to which rare cancers are usually referred, is often limited. We aimed to study the epidemiology of rare cancers in a large population of several countries. METHODS: We analysed survival by age, sex, subsite, and morphology in 57,144 adults with 14 selected rare cancers diagnosed 1983-94. Variations in survival over time and between European regions were also assessed for variations in quality of care. We also estimated the adjusted relative excess risk of death for every rare cancer. FINDINGS: Overall 5-year relative survival was good (ie, >65%) for placental choriocarcinoma (85.4% [95% CI 81.4-89.5]), thyroid medullary carcinoma (72.4% [69.2-75.5]), ovarian germ-cell cancer (73.0% [70.0-76.0]), lung carcinoid (70.1% [67.3-72.9]), and cervical adenocarcinoma (65.5% [64.3-66.6]); intermediate (ie, 35-65%) for testicular cancer at age 65 years or older (64.0% [59.3-68.7]), sarcoma of extremities (60.0% [58.9-61.2]), digestive-system endocrine cancers (55.6% [54.9-56.3]), anal squamous-cell carcinoma (53.1% [51.5-54.8]), and uterine sarcoma (43.5% [42.0-44.9]); low for carcinoma of adrenal-gland cortex (32.7% [28.3-37.2]) and bladder squamous-cell carcinoma (20.4% [18.8-22.0]); and poor for angiosarcoma of liver (6.4% [1.8-11.0]) and mesothelioma (4.7% [4.3-5.2]). Survival was usually better for women than men and poor in those aged 75 years or older. Survival significantly improved over time for ovarian germ-cell cancer, sarcomas of extremities, digestive-system endocrine tumours, anal squamous-cell carcinoma, and angiosarcoma of liver. Survival in northern Europe was higher than in the other geographic groupings for most cancers. INTERPRETATION: Because effective treatments are available for several of the rare cancers we assessed, further research is needed to ascertain why survival is lower in some European countries than in others, particularly in older patients. Audit of best practice for rare cancers with treatment protocols would be useful.

Occupational risks for uveal melanoma results from a case-control study in nine European countries.

OBJECTIVE: Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors. METHODS: A population based case-control study was undertaken during 1995-1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%. RESULTS: Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88-1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma. CONCLUSION: Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing.