Long term activity of vemurafenib in cancers with BRAF mutations: the ACSE basket study for advanced cancers other than BRAFV600-mutated melanoma.

BACKGROUND: BRAF inhibitors are approved in BRAFV600-mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAFV600-mutated melanoma and NSCLC. PATIENTS AND METHODS: Patients with advanced tumours other than BRAFV600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. RESULTS: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAFV600 mutations and 10 with BRAFnonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib. CONCLUSION: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers.

Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study.

BACKGROUND: The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL. METHODS: We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation. RESULTS: A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHRcraftsmen/higher.employment: 4.15 [0.86-20.15]), being a worker or an employee (EHRworkers.employees/higher.employment: 3.57 [1.19-10.7]), having a Binet staging of B or C (EHR: 3.43 [1.84-6.42]) and having a lymphocyte count > 15 G/L (EHR: 3.80 [2.17-6.65]) were statistically associated with a higher risk of excess mortality. EDI was not associated with excess mortality (EHR: 0.97 [0.90-1.04]). CONCLUSION: Socioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.

Rituximab salvage therapy in adults with immune thrombocytopenia: retrospective study on efficacy and safety profiles.

Splenectomy remains the preferred treatment for chronic immune thrombocytopenia (ITP) after corticosteroid failure, despite the risks of despite surgical complications and infection. The aim of this study was to assess the efficacy of and tolerance to rituximab through a retrospective analysis of 35 refractory/relapsing ITP patients treated from 2004 to 2013. The median age of subjects was 46 years (14-80). Rituximab was given at a weekly dose of 375 mg/m(2) for 4 weeks. Median time from diagnosis to first infusion was 17 months (1-362) and follow-up was 47 months (2-133). The overall response rates at 1 and 2 years after the first infusion were 47 and 38 %, with complete response rates of 24 and 25 %, respectively. Median duration of response was 38 months (1-123), with 37 % of patients maintaining a durable response (>1 year). Twenty-nine percent of patients had undergone splenectomy. A durable response after rituximab was more frequently observed in patients undergoing second-line therapy than those in third or later (83 versus 35 %, P = 0.01). Forty-four percent of patients experienced mild hypogammaglobulinaemia after rituximab, and no clinical infection occurred. To conclude, rituximab should be considered as an alternative treatment to splenectomy. Its efficacy and safety profile should lead us to choose this medical option therapy before surgery for ITP patients.

Cancer incidence in France over the 1980-2012 period: Hematological malignancies.

BACKGROUND: The classification of hematological malignancies (HMs) has changed in recent decades. For the first time, the French network of cancer registries (Francim) provides estimates for incidence and trends of HM in France between 1980 and 2012 for major HM subtypes. METHODS: Incidence was directly estimated by modeling the incidence rates measured in the cancer registry area. For each HM subtype, a "usable incidence period" was defined a priori, corresponding to the years for which all the registries collected them in a homogeneous way. For both sexes and each HM subtype, age-period-cohort models were used to estimate national incidence trends. RESULTS: Overall in France, there were an estimated 35,000 new HMs in 2012 (19,400 in men and 15,600 in women). Lymphoid malignancies accounted for more than two-thirds of HM incident cases (n=25,136). The incidence sex ratio (M/F) varied from 1.1 for classical Hodgkin lymphoma to 4.0 for mantle-cell lymphoma. The median age at diagnosis ranged from 62 to 81 years according to the major HM subtypes. Overall in both sexes, the top five most frequent HMs in 2012 were plasma cell neoplasm (about 4900 estimated cases), chronic lymphocytic leukemia/small lymphocytic lymphoma (4500 cases), diffuse large B-cell lymphoma and myelodysplastic syndromes (4100 cases), and acute myeloid leukemia (2800 cases). The incidence rates increased for follicular lymphoma and plasma cell neoplasm during the study period in both sexes. Classical Hodgkin lymphoma was relatively stable in men between 1980 and 2012 and increased in both sexes during the most recent period. Chronic myeloproliferative neoplasms, other than chronic myelogenous leukemia, are the only subtype that showed a slightly downward trend in incidence between 2003 and 2012 in both sexes. CONCLUSION: The striking differences in the incidence patterns by histologic subtype strongly suggest a certain level of etiologic heterogeneity among hematological malignancies and support the pursuit of epidemiologic analysis by subtype for HMs in international studies. Age-standardized incidence rates are essential to analyze trends in risk, whereas the number of incident cases is necessary to make provisions for healthcare resources and to evaluate the overall burden of HM.

Chronic active Epstein-Barr virus infection with cutaneous and sinus lymphoproliferation in a white female patient with 25 years' follow-up: an original case report.

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms associated with very high viral load, as assessed by quantitative polymerase chain reaction. We present an unusual case in a French woman who was followed up over 25 years with cutaneous and sinus lymphoproliferation. This white woman presented with a long history of recurrent cutaneous necrotic papules of the skin, which started during childhood and healed spontaneously with depressed scars. The lesions spread to the left maxillary sinus and were associated with hepatomegaly and splenomegaly with no other visceral locations. Pathological examination of the skin and sinus revealed a dermal monoclonal T-cell lymphoproliferative disorder, CD7(+) and CD20(-) , with no epidermotropism. T-cell receptor rearrangement was positive, showing the monoclonality from the first biopsy. This T-cell proliferation was positive for EBV-encoded small RNA and was associated with a high EBV viral load. Since then, the patient has been in good health, despite a permanently high EBV viral load. Hydroa vacciniforme (HV)-like lymphoma and natural killer/T-cell lymphoma were discussed, but none really fit our case. Natural killer cell lymphoma was ruled out because of the indolent course, but sinus lesions do not exist in HV-like lymphoma. A therapeutic approach is difficult because of the coexistence of viral infection and monoclonal T-cell proliferation. Chemotherapy is not efficient and induces immunosuppression, which may worsen the prognosis. Although rituximab may have an immunomodulatory function, it was not effective in our case.

Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA.

BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0-92 months) for the 227 patients with non-Hodgkin Lymphoma (NHL), with a significant difference between aggressive and indolent NHL (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL patients for whom detailed characteristics were available. Among these patients, 63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was reported as the main cause of death (40%). Treatment administration was associated with improved OS in patients with aggressive (P < 0.001) but not indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia appeared as a strong and independent negative prognostic factor. CONCLUSIONS: The median OS is short in 90+ patients diagnosed with lymphoma but some patients experience prolonged survival. Lymphoma represents the main cause of death in these patients. Treatment may improve survival of selected patients with aggressive but not indolent NHL. Management of these patients may be guided by prognostic factors identified in this study, notably serum albumin.

[Haematological malignancies (HM) in Basse-Normandie (BN): incidence and clinical and biological characteristics over the period 1997-2005 in patients less than 25 years old]. / Épidémiologie des hémopathies malignes en Basse-Normandie : incidence et caractéristiques cliniques et biologiques chez l'enfant et l'adulte jeune de moins de 25ans (1997-2005).

BACKGROUND: The study was designed to present the incidence of all the haematological malignancies (HM) in Basse-Normandie (BN) over the period 1997 to 2005 in patients less than 25 years old. BN is an administrative region in the North-West of France, composed of three departments: Calvados, Manche and Orne. We extracted data from the Registre régional des hémopathies malignes de Basse-Normandie, a French registry which belongs to the Association of the French Cancer Registries (Francim). METHODS: All the HM were coded using the third edition of the International classification for oncologic diseases (ICD-O-3). We compared the clinical and biological descriptive data in patients less than 15 years old to those of young adults (15-24 years old). RESULTS: A total of 305 new cases of HM were recorded over the period 1997 to 2005. HM were more frequent in men (168 cases) than in women (137 cases). Patients less than 25 years old accounted for 4.1% of all HM cases, whereas patients less than 15 years old and young adults (15-24 years old) represented 2.2% and 1.9% of all cases, respectively. In patients less than 25 years old, the overall world-standardized incidence rates (WSR) were 7.67/100,000 (95% CI: 6.31-9.04) in BN (8.08 [6.15-10.02] for men and 7.24 [5.31-9.17] for women). In patients less than 15years, the overall WSR was 7.38/100,000 (6.23-8.52), with no difference between boys (7.57) and girls (7.17). Acute lymphoblastic leukaemia (ALL) was the most frequent HM, WSR=4.02/100,000 (3.16-4.88) (4.30 [3.08-5.53] in men, 3.73 [2.52-4.93] in women), with similar clinical and biological criteria between patients less than 15 years and young adults. In young adults, the overall WSR was 8.21/100,000 (7.47-8.96), similar between men and women (9.02 [7.93-10.12] and 7.37 [6.35-8.38], respectively). Their highest WSR was obtained for Hodgkin lymphomas (HL): 3.37/100,000 (2.89-3.85), similar between men (3.49 [2.8-4.17]) and women (3.25 [2.58-3.93]). The study did not show any significant difference between the Calvados, Manche and Orne departments (except for HL, which seems more frequent in Manche department for 15-24 years old cases). There was no evidence of an increased risk for ALL in the subdistricts Beaumont-Hague and Les Pieux, which respectively have a nuclear waste reprocessing plant and a nuclear power plant on their territory. The subtype of HM was dependent on age whereas clinical and biological data were the same, whatever the age. CONCLUSION: These results contribute to HM monitoring in an area where the nuclear industry is present and to improve the organization and follow-up of medical care.

Guidance for storing blood samples in laboratories performing complete blood count with differential.

INTRODUCTION: The complete blood count (CBC) with differential leukocyte count (DIFF) is an important part of clinical laboratory analyses and provides crucial data for clinicians. Delivery time after blood collection and conditions of storage is known to affect the reliability of results of some hematologic parameters. The aim of this study was to assess the variations of hematologic parameters over time and the influence of storage temperature. METHODS: Blood samples were randomly selected from hospitalized patients and stored at room temperature and at 4 °C. CBC and DIFF were performed on an automated hematology analyzer and the results between the two groups were compared. RESULTS: Samples stored at room temperature showed an important increase in mean corpuscular volume and hematocrit and a decrease in mean corpuscular hemoglobin concentration. Neutrophil counts tended to increase, whereas monocyte counts tended to decrease. CONCLUSION: Storing samples at 4 °C improved reproducibility over time of all quantitative and qualitative parameters. We also observed that NEUT-X, a routine parameter useful in detecting myelodysplastic syndrome, became unreliable when analyzed 24 h after sample collection. Our results led us to recommend that samples should be analyzed within 6 h, particularly if samples are transported at room temperature. We also recommend storing samples at 4 °C in case of remote CBC analysis, especially in the context of clinical trials.

Performance evaluation of the body fluid mode on the platform Sysmex XE-5000 series automated hematology analyzer.

We evaluated the performance of the automated body fluid mode of the Sysmex XE-5000 series automated haematology analyzer and compared the performance of the automated method for obtaining white blood cell (WBC), red blood cell (RBC) counts and WBC differential counts with microscopic method. One hundred and seventy-four samples were analysed: 81 ascitic fluid, 32 cerebrospinal fluid (CSF), 26 pleural fluid (PF), 18 synovial fluid (SF), 13 peritoneal fluid (PeF) and 4 other types. The agreement between the automated method and the manual reference showed high correlation, with Pearson correlation coefficients greater than 0.9 for all types of body fluids. We also demonstrate that the automated body fluid analysis on the XE-5000 is an acceptable alternative to the microscopic reference method as far as ascitic fluid, peritoneal dialysis fluid, SF or PF are concerned. Conversely, results for body fluid samples from oncology patients with leukaemia or tumours showed significant differences between both methods, as XE-5000 counted blast cells and neoplastic cells in mononuclear cell count. XE-5000 could represent an attractive method for the automated analysis of WBC, RBC, mononuclear cell count (MNC) and polymorphonuclear (PMN) cells of most body fluids. However, CSFs from patients with leukaemia or lymphoma should be processed with the microscopic reference method in order to detect abnormal leukaemic cells.

Waved aCGH: to smooth or not to smooth.

Array-based comparative genomic hybridization (aCGH) is a powerful tool to detect genomic imbalances in the human genome. The analysis of aCGH data sets has revealed the existence of a widespread technical artifact termed as 'waves', characterized by an undulating data profile along the chromosome. Here, we describe the development of a novel noise-reduction algorithm, waves aCGH correction algorithm (WACA), based on GC content and fragment size correction. WACA efficiently removes the wave artifact, thereby greatly improving the accuracy of aCGH data analysis. We describe the application of WACA to both real and simulated aCGH data sets, and demonstrate that our algorithm, by systematically correcting for all known sources of bias, is a significant improvement on existing aCGH noise reduction algorithms. WACA and associated files are freely available as Supplementary Data.

[Haematological malignancies: incidence in Basse-Normandie, France, for 1997-2004]. / Epidémiologie des hémopathies malignes en Basse-Normandie.

BACKGROUND: The study was designed to present the incidence of all the haematological malignancies in Basse-Normandie over the period 1997-2004. We extracted the data from the "Registre régional des hémopathies malignes de Basse-Normandie (RRHMBN)", a French registry which belongs to the Association of the French Cancer Registries (FRANCIM). All the malignant haematological diseases were coded using the third edition of the International Classification for Oncologic Diseases (ICD-O-3) and the ADICAP classification, a special version adapted in 2001 for haematology. Five thousand five hundred and ten new cases of malignant haematological disorders were registered over the period 1997-2004. Whatever the department constituting the Basse-Normandie (Calvados, Manche and Orne), no significant difference of incidence was detected. In men, the more frequent malignant disorders were non-Hodgkin's malignant lymphomas (NHML) followed by chronic lymphocytic leukemia and other mature neoplasms, myelodysplastic syndromes (MDS), multiple myeloma (MM), myeloproliferative disorders (MPD), acute myeloid leukemias (AML), Hodgkin's lymphomas (HL), Waldenström's macroglobulinemia (WM) and acute lymphoblastic leukemia (ALL). In women, MM is the third more frequent haematological disorders after NHML and lymphocytic leukaemia and other mature neoplasms, MPD, MDS, AML, Hodgkin's lymphomas, WM and ALL. The other haematological disorders are very rare. We provide the incidence for the main haematological disorders and for the first time we also present the incidence of the different subtypes of the Hodgkin's and non-Hodgkin's malignant lymphomas, mature lymphoid neoplasms, MPD and also MDS. These results are useful for the organization and follow-up of medical care. The development of specialized haematology and active protocols can optimize the management of the older patients. A high quality of the collected data remains necessary for a continuous watching and research on patients with malignant haematological diseases.

[Acquired von Willebrand syndrome: from diagnosis to treatment]. / Le syndrome de Willebrand acquis: du diagnostic au traitement.

Acquired von Willebrand syndrome is a rare bleeding disorder, which has been related in various diseases including lymphoproliferative disorders or autoimmune diseases. Its diagnosis is an important step before treatment of patients and particularly in case of bleeding. We report four cases from Caen Hemophilia Treatment Center, diagnosed and treated from 1999 to 2008. Mucocutaneous bleeds in every case were the same as in hereditary von Willebrand disease. All patients had no personal or family history of bleeding. Phenotype was identified as type 2 von Willebrand disease with a loss of high molecular weight multimers. Anti-von Willebrand factor inhibitor screening was positive for three patients. The etiological diagnosis was one chronic lymphocytic leukaemia, two monoclonal gammapathies of undetermined significance (MGUS) and one undetermined case. The management of patients need two stages: first infusions of factor von Willebrand/factor VIII concentrates to stop bleeds, then treatment of the underlying disease such as chemotherapy, corticotherapy and treatment with high doses of polyvalents immunoglobulins. In every case, treatment was effective and improved patient's quality of life.

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease.

CD4+CD56+ haematodermic neoplasms (HDN) constitute a rare disease characterized by aggressive clinical behaviour and a poor prognosis. Tumour cells from HDN are leukaemic counterparts of plasmacytoid dendritic cells (pDCs). Despite increased knowledge of the ontogenetic origin of these tumours, the genetic causes and oncogenic signalling events involved in malignant transformation are still unknown. To delineate novel candidate regions and disease-related genes, we studied nine typical CD4+CD56+ HDN cases using genome-wide high-resolution array comparative genomic hybridization (CGH). Genomic imbalances, which were predominantly losses, were frequently detected. Gross genomic losses or gains involving an entire chromosome were observed in eight cases. The most frequent imbalances were deletions of chromosome 9, chromosome 13 and partial losses affecting 17p or 12p. Combinations of deletions of tumour suppressor genes (TSG), namely RB1, CDKN1B (p27), CDKN2A, (p16(ink4a), p14(arf)) or TP53 (p53), were observed in all cases. These results indicate that deletion events altering G1/S regulation are crucial for HDN oncogenesis. Furthermore, in addition to frequent sporadic gene losses, in one case we observed a 8q24 interstitial deletion that brought MYC closer to miR-30b/miR-30d, which may be related to their deregulation. Taken together, these results indicate that in addition to frequent G1/S checkpoint alterations, various genetic events could contribute to the chemoresistance of the tumour.

Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study.

OBJECTIVES: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LNs) in men. METHODS: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of LN aged 18-75 years. During the same period, controls of the same age and sex as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPSs) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (ORs) and 95% CI were estimated using unconditional logistic regressions. RESULTS: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR = 8.4 (2.2 to 32.4), 10.8 (2.4 to 48.1), respectively). Exposure to insecticides, fungicides and herbicides were linked to a threefold increase in MM risk (OR = 2.8 (1.2 to 6.5), 3.2 (1.4 to 7.2), 2.9 (1.3 to 6.5)). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR = 4.9 (1.1 to 21.2), 4.1 (1.1 to 15.5), 5.1 (1.4 to 19.3)), although based on small numbers. Lastly, despite the increased ORs for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. CONCLUSIONS: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.

Performance evaluation and relevance of the CellaVision DM96 system in routine analysis and in patients with malignant hematological diseases.

The CellaVisiontrade mark DM96 is an automated image analysis system dedicated to locating and preclassifying the various types of white blood cells in peripheral blood smears. The system also partially characterizes of the red blood cell morphology and is able to perform platelet counts. We routinely analyzed the blood samples from 440 patients with quantitative and/or qualitative abnormalities detected by the XE-2100 Sysmextrade mark. Only 2.6% of cells are not identified by DM96trade mark. After classification of the unidentified cells very good correlation coefficients are observed between DM96trade mark and manual microscopy for most hematological parameters and accuracy is judged excellent up to 98%. For most common parameters, false positive and false negative ratios are also very good. Whatever the pathology and the number of blasts on smear, all patients were positive for blast detection on DM96trade mark. The system is a useful tool for assisting in the diagnosis and classification of most acute or chronic leukemia. Automatic cell location and preclassification, along with unique cell views on the computer screen, could reduce the time spent performing differentials and make real-time collaboration between colleagues a natural part of the classification process. The workstation also provides an ergonomically correct and relaxed working environment. We suggest its use in routine analysis; the system could be very helpful for the accurate morphological diagnosis of samples from patients with malignant hematological disease.

Cigarette smoking, alcohol drinking, and risk of lymphoid neoplasms: results of a French case-control study.

OBJECTIVE: To study potential role of smoking and alcohol in lymphoid neoplasms (LN). METHODS: A case-control study that included 824 cases and 752 hospital controls aged 18-75 years was conducted. Cases were newly diagnosed with non-Hodgkin's or Hodgkin's lymphoma, multiple myeloma, or lymphoproliferative syndrome (LPS). Controls were matched with the cases by gender, age, and center. RESULTS: Overall, smoking was not related to LN. However, average tobacco consumption tended to be inversely related to non-Hodgkin's lymphoma (NHL), LPS, and the hairy cell leukemia (HCL) subtype, with a significant negative trend for the latter (OR of 0.4, 0.2, 0.1 for consumptions of 20 cig/day). An inverse association between 'ever drinking' and Hodgkin's lymphoma (HL: OR = 0.5 [0.3-0.8]) and NHL (OR = 0.7 [0.5-1.0]) was evidenced and restricted to the diffuse large B-cell lymphoma subtype, with significant negative trends. The controls' smoking and drinking habits were similar to those of French population. The results remained unchanged after adjustment for potential confounding factors and when smoking and drinking were both included in the models. CONCLUSION: Results are consistent with those of several previous studies and suggest a direct or indirect protective effect of smoking with respect to HCL although based on small numbers. The negative relationship between alcohol consumption and Hodgkin's and NHL, also previously reported, needs further investigations.

Cancer incidence and mortality in France over the period 1980-2005.

BACKGROUND: The objective of this study was to provide updated estimates of national trends in cancer incidence and mortality for France for 1980-2005. METHODS: Twenty-five cancer sites were analysed. Incidence data over the 1975-2003 period were collected from 17 registries working at the department level, covering 16% of the French population. Mortality data for 1975-2004 were provided by the Inserm. National incidence estimates were based on the use of mortality as a correlate of incidence, mortality being available at both department and national levels. Observed incidence and mortality data were modelled using an age-cohort approach, including an interaction term. Short-term predictions from that model gave estimates of new cancer cases and cancer deaths in 2005 for France. RESULTS: The number of new cancer cases in 2005 was approximately 320,000. This corresponds to an 89% increase since 1980. Demographic changes were responsible for almost half of that increase. The remainder was largely explained by increases in prostate cancer incidence in men and breast cancer incidence in women. The relative increase in the world age-standardised incidence rate was 39%. The number of deaths from cancer increased from 130,000 to 146,000. This 13% increase was much lower than anticipated on the basis of demographic changes (37%). The relative decrease in the age-standardised mortality rate was 22%. This decrease was steeper over the 2000-2005 period in both men and women. Alcohol-related cancer incidence and mortality continued to decrease in men. The increasing trend of lung cancer incidence and mortality among women continued; this cancer was the second cause of cancer death among women. Breast cancer incidence increased regularly, whereas mortality has decreased slowly since the end of the 1990s. CONCLUSION: This study confirmed the divergence of cancer incidence and mortality trends in France over the 1980-2005 period. This divergence can be explained by the combined effects of a decrease in the incidence of the most aggressive cancers and an increase in the incidence of less aggressive cancers, partly due to changes in medical practices leading to earlier diagnoses.