Survival of cancer patients in France: a population-based study from The Association of the French Cancer Registries (FRANCIM).

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.

A population-based assessment of the prognostic value of the CD19 positive lymphocyte count in B-cell chronic lymphocytic leukemia using Cox and Markov models.

No population-based study has assessed the prognostic impact on survival of the CD19 positive lymphocyte count, evaluated by immunophenotyping at diagnosis, in B-cell chronic lymphocytic leukemia (B-CLL). Aiming at addressing this issue, we investigated the clinical outcome of a well-defined population of B-CLL patients. Survival of B-CLL patients, diagnosed between 1990 and 1999 and recorded by the Registry of Hematological Malignancies of the Côte d'Or, was analysed applying Cox's regression model to the 237 included cases and to the 195 Binet stage A patients. To assess simultaneously the predictive value of each parameter on the risk of disease progression and on the risk of death, we completed this analysis by applying a three-states homogeneous Markov model to the whole study population. Analysis of the entire population showed that age (p < 0.001), Binet stage (p = 0.008) and CD19 positive lymphocyte count (p = 0.038) were three independent prognostic factors. However, in stage A patients, only progression into a more advanced stage, analysed as a time-dependent variable, and age had a clear impact on survival (p < 0.001 for both). Markov model revealed that an increased CD19 positive lymphocyte count increased the risk of disease progression in stage A patients (p = 0.002) but did not have direct impact on survival of either stage A patients with stable disease or stage B or C patients. An increased CD19 positive lymphocyte count at diagnosis is a marker of an increased risk of disease progression in stage A patients. Thus, it can be a useful tool for the clinical management of these patients.

EUROCARE-3: survival of cancer patients diagnosed 1990-94--results and commentary.

EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central-southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin's lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation's health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.

Therapy-related acute promyelocytic leukemia.

PURPOSE: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. PATIENTS AND METHODS: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. RESULTS: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. CONCLUSION: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

[Evolution of eosinophilia during the pollen season among the general population: a way of determining new sensitiziations]. / Evolution de l'eosinophilie au cours de la saison pollinique dans la population generale: un outil pour determiner de nouvelles sensibilisations.

The purpose of this paper was to verify the effect of pollen peaks on blood eosinophilia in an all and sundry population, including allergic as well as non-allergic subjects, so that we can open up new horizons in the understanding and prevention of pollinosis. Daily eosinophilia counts of hospital patients were measured at the time of a blood checkup (1996-1998), and divided into six classes. Those data were compared to daily pollen counts of twelve taxa, coming from the Hirst trap of Dijon (France). An eosinophilia increase occurred when hazel, hornebeam, birch, oak, grasses, ragweed and plantain were present in high concentration. In other cases, only simultaneous presence of several taxa seemed to play a part, because of cross-reactivity or polysensitization. Lastly, Cupressaceae-Taxaceae and ragweed were seen as increasing eosinophilia in seemingly non allergic people. The analysis of eosinophilia in the general population was able to reveal potential allergic patients and potential allergic diseases.

Minor dysplastic changes are frequently observed in the bone marrow aspirate in elderly patients without haematological disease.

Bone marrow aspirates were obtained by sternal puncture prior to sternotomy in 54 volunteers (40 males and 14 females) aged 60 years or more. All underwent surgery for cardiological diseases and had normal blood counts, without any haematological abnormalities. Quantitative examination of these bone marrow aspirates yielded reference ranges for each cell type similar to those obtained in younger adults. However, qualitative analysis revealed certain discrepancies: dysplastic changes were observed frequently, mainly in megakaryocytes and erythroblasts, with a normal growth pattern of haematopoietic progenitor cells. A low proportion of macrophages and mast cells were noted in 30% of the bone marrow aspirates. Lymphoid aggregates, seen in 13% of these samples, were generally of moderate size, contained few mast cells and were non-clonal on immunophenotypic analysis.

Acute myeloid leukemia with hypergranular cytoplasm: a differential diagnosis of acute promyelocytic leukemia.

We report here the case of a woman with acute myeloid leukemia with some blast cells exhibiting acute promyelocytic leukemia (APL)-like hypergranular cytoplasm. The cytologic and cytochemical aspects as well as the mature myeloid phenotype and hemostasis disorders were consistent with the diagnosis of APL. However, no t(15;17), or RARalpha gene, MLL gene or PML gene rearrangement was observed, or any other cytogenetic clonal abnormality. Coexpression on blast cells of CD33 and CD56 without CD34, CD16 or HLA-DR, suggested a myeloid/natural killer cell acute leukemia.

Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: a population-based study.

PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d'Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area. RESULTS: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P <.0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses >/= 13 mg/m(2). CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.

National cancer prevalence estimation in France.

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.

Increase therapy-related leukemia secondary to breast cancer.

Therapy-related leukemia associated with chemotherapy, particularly alkylating agents and topoisomerase II inhibitors, are being reported with increasing frequency in the literature mainly after breast cancer. We also observed an increasing number of such leukemias in the data base of the specialized registry of hematological malignancies of the Côte d'Or department. Between 1980 and 1998, 156 AML and RAEB-t were registered in women in Côte d'Or. Among them, 12 occurred in women with breast cancer history (7.7%). Analysis by period of time shows a significant increase in the proportion of therapy-related leukemia secondary to breast cancer (P < 0.02). Chemotherapy including topoisomerase II inhibitors was used in 10 cases in which mitoxantrone was used in eight cases. In these eight cases, leukemia had clinical and biological characteristics usually described with topoisomerase II inhibitors but 44% were promyelocytic sub-type with the t(15;17) specific karyotypic abnormality. These data on a well-defined population demonstrate the increased proportion of therapy-related leukemia secondary to breast cancer, probably due to the use of mitoxantrone.

Immunophenotype of a transient myeloproliferative disorder in a newborn with trisomy 21.

Cytologic, immunologic, and cytogenetic studies were performed on the blast cells of a newborn with Down syndrome and transient myeloproliferative disease. This hematologic disorder is uncommon, and occurs primarily in infants with Down syndrome. This boy presented with a high white blood cell count and a high percentage of blast cells, without anemia or thrombocytopenia. Chromosome analysis showed a constitutional trisomy 21 without any other clonal abnormality. A three-color flow cytometric analysis was performed and revealed two different CD45 dim, CD34(+), CD117(+), CD56(+) immature subpopulations: the normal immature myeloid precursor and an immature blast cell population that expressed CD41, CD42, CD61, CD36, CD13, CD1a, and CD2. We postulate that this population could be the leukemic precursor involved in the acute megakaryoblastic leukemia frequently observed in children with Down syndrome.

The rise in incidence of lymphomas in Europe 1985-1992.

A collaborative study was carried out of the descriptive epidemiology of the lymphomas from seven countries across Europe in the period 1985-1992. Careful attention was paid to sources of information and the data quality in close collaboration with expert histopathologists. The data were classified as non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). An attempt was made to put the data into a modified version of the Revised European American Lymphoma (REAL) classification. We observed an overall rise in total NHL throughout the time period in all European countries but no such trend in HD. The increase in NHL overall being 4.2% per annum, representing an increase of 4.8% in males and 3.4% in females per annum, was only marked in middle and old age. Such increases were observed in all participating areas except in Burgundy. Different countries, however, have different base rates, the rates being highest in Scandinavia and the Netherlands. The analysis by subcategory classification suggested that the increase in NHL was confined to the follicle centre cell type, extranodal B-cell, nodal T-cell and nodal lymphomas not otherwise specified, categories. These new observations present a picture of real increase in case incidence with no obvious explanation. The increases in NHL do not appear to be due solely to better diagnoses. Pending other explanations or refutation, these present a compelling picture of an inexorable rise in incidence of this disease.

Population density and childhood leukaemia: results of the EUROCLUS Study.

The EUROCLUS study assembled incidence data for 13,551 cases of childhood leukaemia (CL) diagnosed between 1980 and 1989 in 17 countries (or regions of countries). These were referenced by location at diagnosis to small census areas of which there were 25,723 in the study area. Population counts, surface area and, hence, population density were available for all these small areas. Previous analyses have shown limited extra-Poisson variation (EPV) of case counts within small areas; this is most pronounced in areas of intermediate population density (150-499 persons/km2). In this study, the data set was examined in more detail for evidence that variations in incidence and EPV of CL are associated with population density. Incidence showed a curvilinear association with population density and was highest in areas which were somewhat more densely populated (500-750 persons/km2), where the incidence rate ratio relative to areas having > or = 1000 persons/km2 was 1.16 (95% confidence interval 1.07-1.26) and the P value for quadratic trend across eight strata of population density was 0.02. Incidence in these areas is uniformly elevated and showed no evidence of heterogeneity (i.e. EPV). Statistically significant evidence of EPV was evident amongst some of the areas previously classified as intermediate density areas (specifically, those with a density of 250-499 persons/km2, P < 0.001 for CL). These results were interpreted in terms of the current aetiological hypotheses for CL which propose that exposure to localised epidemics of one or more common infectious agent may contribute to the development of leukaemia. They suggest that such epidemics arise regularly in moderately densely populated areas and also sporadically in areas which are somewhat less densely populated. Although other interpretations are possible, these results may assist in the identification of characteristics which infectious agents must possess if direct or indirect causes of CL.

Residential magnetic field measurements in France: comparison of indoor and outdoor measurements.

Residential magnetic field (MF) measurements were performed for the first time in a representative sample of French dwellings. Exposure levels were assessed by two methods: indoor and outdoor measurements. Linear and logistic regression models were used to determine factors associated with the time-weighted average (TWA) home MF. TWA magnetic field magnitudes were approximately log-normally distributed with geometric means under 0.010 microT for both indoor and outdoor measurements. Only 5% of the dwellings presented indoor MF levels greater than 0.120 microT (1.2 mG). Both indoor and outdoor MF variations were explained by three factors: wiring configuration, the dwelling's location (i.e., urban or rural), and housing characteristics (individual houses or apartment building). The reliability of outdoor spot measurements with 30-min bedroom recordings was assessed by an intraclass correlation coefficient. The measurements were accurate in rural areas and small towns. In urban centers, local MF variations spoil the outdoor measurement's reliability. If indoor measurements are taken as the reference method, the use of outdoor instead of indoor measurement leads to an important decrease in statistical power. Further assessment of MF near high power transmission lines is necessary to evaluate the usefulness of outdoor spot recordings near such lines. The urban MF environment also has to be explored to identify extraneous sources.

Testing the proportional hazards assumption in medical survival studies--application to a population-based study of acute myeloid leukaemia.

BACKGROUND: In the analysis of survival data using the Cox proportional hazard model, it is assumed that the magnitude of mortality risk for a predictor variable remains proportional over time. The time-dependent linear model and the piece-wise proportional hazard model (two or four intervals) take into account the variation of the risk over the entire follow-up period. METHOD: The three existing models were applied to a series of 266 patients with acute myeloid leukaemia (AML), diagnosed between 1980 and 1992 and recorded by the Registry of Hematopoietic Neoplasms in Côte d'Or, France. RESULTS: A non-proportional effect of age, period of diagnosis, whether the illness was primary or secondary and French-American-British (FAB) subtype was found significant. In particular, the effect of M2 versus M4-M5 subtypes was revealed by the non-proportional analyses, although this effect was non-significant using the Cox model. CONCLUSIONS: The clinical explanation of the variation of these effects over time is discussed, for example, relating the increase over time of the positive effect of the period of diagnosis to therapeutic improvements. Confirmation of these results on an independent data set is required.

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction.

Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H2O2. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24-96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 +/- 0.80 (T0) to 4.57 +/- 1.24 (peak), and decreased to 2.96 +/- 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.7 +/- 7.5 hours. The iron increased significantly from 0.67 +/- 0.34 (T0) to 1.15 +/- 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 +/- 0.28 UI/L at T48 (TO vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.4 +/- 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.