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Background: Little is known about the economic burden of pretherapeutic staging of patients presenting colorectal cancer metastases., Objective: The aim of this study was to estimate the cost of pretherapeutic staging and identify cost determinants for 132 patients presenting colorectal metastases and living in the north-east of France., Method: Staging cost was estimated using direct medical costs from the point of view of the French Health Insurance System. Independent factors were identified using a linear regression model, and bootstrap resampling was used to estimate unbiased standard errors and 95% confidence intervals., Results: The overall mean cost for pretherapeutic staging was estimated to be 1534€ [95% CI: 1250€-1818€]. Staging costs increased significantly with the number of medical procedures performed during the staging, and according to health care patterns (in-patient hospital stay versus out-patient episodes, public versus private care)., Conclusion: These results could now be used to estimate the impact of new imaging techniques on clinical practices and pretherapeutic staging costs., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Purpose: This prospective multicenter study explored different definitions of time to deterioration (TTD) in quality of life (QoL) scores, according to different cutoffs of the minimal clinically important difference (MCID) as a modality for longitudinal QoL assessment in breast cancer patients., Methods: QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and BR-23 before surgery, after surgery, and 6 and 12 months later. The global health score, arm symptoms score (BRAS), and breast symptoms score were analyzed. For a given baseline score, QoL was considered to have deteriorated if this score decreased by ≥5 points at any time point after baseline. Analyses were repeated using an MCID of 10 points and taking the score after surgery as the reference score (to explore the occurrence of response shift). TTD was calculated using the Kaplan-Meier method and Cox regression was used to identify independent factors associated with TTD., Results: Two hundred thirty-five patients underwent axillary lymph node dissection (ALND), 222 underwent sentinel lymph node biopsy (SLNB), and 61 underwent SLNB plus ALND. Patients who underwent SLNB had a significantly longer TTD for the BRAS dimension than those who underwent ALND. Cox multivariate analyses showed that treatment using SLNB and age >59 years were independently associated with longer TTD for the BRAS, whereas surgery elsewhere than at the Centre Georges François Leclerc was associated with a shorter TTD., Conclusion: Exploration of different definitions of TTD in QoL provides meaningful longitudinal QoL results for clinicians.

Background: The aim of this population-based study was to assess independent prognostic factors in ovarian cancer using relative survival (RS) and to investigate changes in RS rates from 1982 to 2005., Methods: Data on 748 patients with ovarian cancer were provided by the Côte d'Or gynaecologic cancer registry. The RS was estimated using a generalized linear model with a Poisson error structure. Relative survival and its 95% confidence interval (CI) were described at the following specific time points 1, 3 and 5 years. The effect of prognostic factors on survival was assessed with multivariate analyses of RS., Results: The median follow-up was 12 years. The RS rates at 1, 3 and 5 years were 81%, 55% and 44%, respectively. As compared with the period 1982-1989, an improvement in survival was found for the period 1998-2005: HR = 0.52[0.40-0.67]. Women who lived in urban areas had better RS: HR = 0.82[0.67-0.99]. Patients with epithelial types of ovarian cancer other than mucinous or endometrioid cancer had worse RS than those with serous histology. Age ≥ 70 years was associated with lower survival., Conclusions: Period of diagnosis, stage at diagnosis, histology, place of residence and age were independent prognostic factors for survival in ovarian cancer. An improvement in the survival rate was observed after 1998 but a significant improvement was limited to advanced stage cancers.

This work presents a brief overview of Markov models in cancer screening evaluation and focuses on two specific models. A three-state model was first proposed to estimate jointly the sensitivity of the screening procedure and the average duration in the preclinical phase, i.e. the period when the cancer is asymptomatic but detectable by screening. A five-state model, incorporating lymph node involvement as a prognostic factor, was later proposed combined with a survival analysis to predict the mortality reduction associated with screening. The strengths and limitations of these two models are illustrated using data from French breast cancer service screening programmes. The three-state model is a useful frame but parameter estimates should be interpreted with caution. They are highly correlated and depend heavily on the parametric assumptions of the model. Our results pointed out a serious limitation to the five-state model, due to implicit assumptions which are not always verified. Although it may still be useful, there is a need for more flexible models. Over-diagnosis is an important issue for both models and induces bias in parameter estimates. It can be addressed by adding a non-progressive state, but this may provide an uncertain estimation of over-diagnosis. When the primary goal is to avoid bias, rather than to estimate over-diagnosis, it may be more appropriate to correct for over-diagnosis assuming different levels in a sensitivity analysis. This would be particularly relevant in a perspective of mortality reduction estimation.

Objectives: The aim of this study was to compare the cost and the effectiveness of two biennial fecal occult blood screening tests for colorectal cancer: a guaiac nonrehydrated test (G-FOBT) and an immunochemical test (I-FOBT) with the absence of screening., Methods: A Markov model was developed to compare these strategies in a general population of subjects aged 50 to 74 over a 20-year period., Results: Compared with the absence of screening, G-FOBT and I-FOBT were associated with a decrease in colorectal cancer mortality of 17.4 percent and 25.2 percent, respectively. With regard to cost-effectiveness, expressed as cost per life-year gained, I-FOBT was the most effective and most costly alternative. Compared with no screening, G-FOBT and I-FOBT presented similar discounted incremental cost-effectiveness ratios: 2,739 euros and 2,819 euros respectively per life-year gained. When compared with G-FOBT, I-FOBT presented an incremental cost-effectiveness ratio of 2,988 euros per life-year gained. Sensitivity analyses showed the strong influence of the I-FOBT lead time, of the participation rate to screening for I-FOBT, and of the purchase price of the I-FOBT on the discounted incremental cost-effectiveness ratios., Conclusions: Compared with the absence of screening and with G-FOBT, the biennial two-stool immunochemical test can be considered a promising method for mass screening for colorectal cancer.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

Background: This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients., Patients and Methods: The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal-Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL., Results: Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores were similar whatever the surgical procedure: sentinel node biopsy (SLNB), axillary node dissection (ALND) or SLNB + ALND. As compared with other surgical groups, GHS 75.91 [standard deviation (SD) = 17.44, P = 0.041] and BRAS 11.39 (SD = 15.36, P < 0.0001) were better in the SLNB group 12 months after surgery. Whatever the type of surgery, GHS decreased after surgery (P < 0.0001), but increased 6 months later (P = 0.0016). BRAS symptoms increased just after surgery (P = 0.0329) and until 6 months (P < 0.0001) before decreasing (P < 0.0001)., Conclusions: SLNB improved GHS and BRAS QoL in breast cancer patients. However, surgeons must be cautious, SLNB with ALND results in a poorer QoL.

Background: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization., Methods: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management., Results: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups., Conclusion: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches.

A field enquiry mentioned the potential positive impact of a feed restriction on the health of young rabbits, but no objective information relates the intake to digestive health. The effects of a post-weaning feed restriction strategy were thus studied on digestive health and growth and carcass parameters of the growing rabbit, using a monofactorial design that produces a quantitative linear reduction of the intake, from ad libitum (AL group) to 80%, 70% and 60% of AL. The study was performed simultaneously in six experimental sites, on 1984 growing rabbits (496 per treatment) collectively caged from weaning (34 to 38 days of age, depending on the site) to slaughter (68 to 72 days). The feeding programme was applied as followed: restriction during 21 days after weaning, and then ad libitum till slaughter. During the feed restriction period the growth rate was linearly reduced with the restriction level, by 0.5 g/day for each percent of intake reduction. When returning to ad libitum intake (after 54 days old) a compensatory growth and a higher feed efficiency occurred. Therefore, the impact of the feeding programme on the slaughter weight (SW) was significant (-4.5 g/% of restriction), but relatively moderate: the weight loss of the more-restricted rabbits (60%) reached 7.7% (-200 g) compared to the AL group. Over the whole fattening period, the feed restriction reduced linearly and significantly the feed conversion (FC) (-0.0077 unit/% of restriction). Carcass traits were little affected by the feeding programme, except for a slightly lower decrease of the dressing percentage (mean: 1.2 units between AL and the three restricted groups). On the six experimental sites, mortality and morbidity were always caused by acute digestive disorders, namely diarrhoea and/or caecal impaction. Independent of the treatment, the mortality rate strongly varied according to the site (between 7% and 18% from weaning to 54 days and for the AL group). During feed restriction, the mortality was significantly lower from a restriction threshold of 80% (meanly: -9% compared to AL). The morbidity was also significantly reduced (-6%) for the two most restricted groups (70% and 60%). The favourable effect of a lower intake on health did not persist after returning to ad libitum intake (54 days to slaughter), since mortality and morbidity were not significantly different among the treatments. Such a feeding strategy thus represents a double benefit in terms of feed costs and lower losses of young rabbits.

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.

Background: The process of diagnosis and management of solitary pulmonary nodules (SPNs) between 1 and 3 cm is not standardized. This multicentre study investigated how diagnosis of newly discovered SPNs is managed in routine practice., Methods: We examined 11,515 radiology reports of patients undergoing chest computed tomography (CT) at all 76 radiology centres in 18 French administrative districts covering 8,220,000 people. Information on diagnostic procedures and treatment administered from discovery to definitive diagnosis of SPN was collected prospectively., Results: We identified 152 cases of newly diagnosed SPNs. Follow-up was complete for 112 patients. The median number of diagnostic tests was 4 and the mean time to diagnosis was 41.4 days. Marked variability was observed in the sequence of diagnostic tests, and 8 diagnostic pathways were identified. Patients' characteristics and radiological features of SPNs influenced the number of tests performed. Referral by specialist, history of smoking and spiculated SPN predicted the performance of at least one invasive procedure (P < 0.01). Definitive diagnosis was a malignant disease in 30 patients (26%)., Conclusion: The diagnosis of SPN is a complex process that physicians approach in markedly different ways. Implementing practice guidelines for managing the diagnosis of SPN requires clarification.

Background: Few population-based studies have reported jointly analyses of relative survival according to the following prognostic factors: tumour-node-metastasis (TNM) stage, age, number of examined and positive nodes, hormonal status, histological Scarff, Bloom and Richardson (SBR) grade, tumour extension, hormone receptor status and tumour multifocal status., Patients and Methods: Data on female invasive breast cancer were provided by the Cote d'Or breast cancer registry. The Kaplan-Meier method and log-rank test were used to estimate and compare the survival probability at 1, 5, 10 and 15 years. The effect of prognostic factors on survival was assessed with crude and relative multivariate survival analyses., Results: Crude survival seemed to be worse in patients aged >60 years compared with those aged 45-60 (P > 0.0001), whereas relative survival did not differ. TNM stage, histological SBR grade, progesterone receptor status, tumour multifocal status, locoregional extension and the period of diagnosis were independent prognostic factors of crude and relative survival., Conclusion: Breast cancer is influenced by many factors. Despite the absence of any association between the number of examined nodes and overall survival in this study, the number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.

Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival.

Purpose: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer., Experimental Design: Breast biopsies from 93 HER-2-positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+., Results: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors., Conclusions: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.

Introduction: Several studies have suggested that rurality is a risk factor for worse prognosis in cancer., Methods: The study population included the 2268 lung cancer cases collected between 1981 and 1996 in the Doubs Cancer Registry (France)., Results: The numbers of patients were 849 (31.8%) in rural areas and 89 (3.3%) in very rural areas. The relative 5-year survival was 15.2% in rural areas and 13.4% in urban areas (p = 0.5), and 2.7% in very rural areas and 14.4% in extended urban areas (p = 0.02). Multivariate analyses of observed and relative survival showed that patients living in very rural areas (p < 0.0001), 65 years of age and older and having small cell carcinoma had a significantly shorter survival., Conclusions: This study showed that the multidimensional definition of rurality identified a population with unfavorable prognoses.

Trastuzumab (Herceptin), a recombinant, humanised, monoclonal-antibody that targets human epidermal growth factor receptor 2 (HER2), has been approved as an adjuvant therapy for HER2-positive early breast cancer. The aim of this study was to assess the incremental cost-effectiveness ratio of this treatment compared with adjuvant therapy alone in the French setting. A cost-effectiveness analysis was performed using a Markov state transition model. The transition probabilities were estimated from the interim results of the Hera trial. Unit costs data were mainly estimated in a French Oncology Center (Georges-François Leclerc, Dijon). The model estimated that overall mean survival of patients treated with trastuzumab was 20.08 years versus 16.23 in the observation group (3.85 life-years gained). For 1 000 patients with a 10-year follow-up, an adjuvant therapy with trastuzumab would avoid 49.7 loco-regional recurrences, 179.5 distant recurrences and 133.4 deaths. The incremental discounted cost of trastuzumab therapy over a lifetime horizon was estimated at 27594 euro per patient in association with a discounted gain of 2.27 life-years. In accordance with the techniques of economical evaluation, the utilization of trastuzumab as an adjuvant therapy in patients with early HER2 positive breast cancer improves patient survival with an acceptable cost-effectiveness ratio in the French setting (incremental cost-effectiveness ratio of 12,148 euros /LYG).

The objective of this study was to estimate the direct costs of invasive cervical cancer (ICC) management to the French national health insurance system the 1st year after ICC diagnosis. A retrospective survey was conducted in three centres in 2005, including 42 patients admitted for ICC between 2001-2003. Medical records were examined for data relating to treatments and to determine the management costs. To estimate the annual cost of ICC management in France, data were extrapolated to the general population. The number of new ICC cases in France was estimated at 3,247 in 2003. The mean hospitalisation cost increased with ICC severity at diagnosis: 9,164 euros for stage I, 15,999 euros for stage II, 22,697 euros for stage III, and 26,886 euros for stage IV. The annual cost associated with the medical management of ICC patients was estimated at 43,862,125 euros (sensitivity range 32,973,461 euros-54,748,422 euros) corresponding to a mean patient cost of 13,509 euros. Recent HPV vaccination studies have shown 100 % for a quadrivalent (6,11,16,18) HPV vaccine against HPV-induced carcinoma in situ (FIGO stage 0/CIN3), a precursor lesion that may develop into ICC. Thus, it is expected that this vaccine will significantly reduce the socio-economic burden associated with this disease.

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.

The definition of appropriate use of drugs is questioned in oncology. Daily therapeutic practices were compared to official labelling and to published scientific data in this retrospective study. It was carried out in two respective specialised centers, from January to September 2004. All chemotherapies administered for adult solid tumours and including one of the eleven studied drugs were evaluated. The analysis of use was performed by drug : conformity to the validated labelling and level of scientific evidence (at the period study). The study included 1,561 drug uses in 1,211 patients. The overall rate of conformity to official labelling was 81.7 % (67.1 % of strict conformity). In 73.8 % of cases, the indications were supported by at least one randomized phase III trial. The results appeared to be significantly different in rare tumours. The potential economic stake of the "contrat de bon usage" was estimated as less than 5 % in our study. This analysis showed an appropriate and controlled use of onerous drugs in solid tumours. The official labelling of drugs are unable to answer to all clinical situations. The definition of a sufficient level of evidence is mandatory for the use of scientific data in clinical practice. This process has to be adapted for rare tumours.

The confrontation of the macro- and micro-economic approaches of hospital costs is a recurrent question, in particular for pathologies where length of stay is highly variable, like acute myeloid leukemias (AML). This monocentric and retrospective study compares direct hospital medical costs of induction and relapse treatment sequences for AML, valued according to four different approaches: the analytic accounting system of our hospital, the French Diagnosis Related Group (DRG) cost databases of hospital discharges (readjusted, or not, to actual hospital stay duration), and official tariffs from the new French DRG prospective payment system. The average cost of hospital AML care valued by the analytic accounting system of our hospital is 61,248 euros for the induction phase and 91,702 euros for the relapse phase. All other national valuation methods result in a two- to four-fold underestimation of these costs. Even though AMLs are now individualized in the 10th version of the French diagnosis related group (DRG) classification, the impact of this issue in other pathologies is going to increase with the gradual implementation of the French DRG prospective payment system. That is why it must be assessed before the progressive extension of this financing system.

Objectives: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research., Methods: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed., Results: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist's diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers' compensation., Conclusions: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.

Background: The aim of the study was to compare the longitudinal quality of life (QoL) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a randomized multicenter phase III trial (FFCD 9102)., Materials and Methods: All patients with locally advanced resectable (T3-4 N0-1 M0) epidermoid or glandular esophageal cancer (n = 451) received induction chemoradiation. Responders (n = 259) were randomized between surgery (arm A) and continuation of chemoradiation (arm B). The Spitzer QoL Index was scored (0-10) at inclusion and at each follow-up, every 3 months during 2 years. QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements. The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up., Results: The squamous histology was predominant in both arms. The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups. QoL scores at the first follow-up were comparatively worse in arm A than in arm B (7.52 versus 8.45, P < 0.01), whereas the longitudinal QoL study showed no difference between treatments (adjusted P = 0.26). Furthermore, the longitudinal QoL was not different (adjusted P = 0.23) among survivors with 2 years of follow-up., Conclusions: Among patients responding to induction chemoradiation, surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced, resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period.

Objective: We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma., Subjects and Methods: A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight., Results: Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3; 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation., Conclusion: It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved.

Unlabelled: Few data exist on the medicoeconomic usefulness of PET in the management of metachronous liver metastases from colorectal cancer. This study was designed to assess the cost-effectiveness of PET in the diagnosis and staging of patients with metachronous liver metastases of colorectal cancer using a decision analysis model., Methods: Two alternatives were compared: CT and CT associated with PET (CT+PET). Transition probabilities were estimated from published data and consultations with experts. Survival data were provided by the Burgundy Digestive Cancer Registry (France). Costs of imaging techniques and treatments were assessed using reimbursements from the French health care insurance for the year 2004. Evaluation criteria included incremental cost-effectiveness ratios and the proportion of unnecessary operations avoided in patients without metachronous liver metastases., Results: CT+PET was the most cost-effective strategy, presenting an expected incremental cost saving of 2,671 (approximately $3,213) per patient, for the same level of expected effectiveness as CT alone (1.88-y life expectancy per patient). Sensitivity analyses performed on epidemiologic and economic parameters showed that this model was robust. The model also suggested that CT+PET could avoid exploratory surgery for 6.1% of patients-that is, 88.4% risk reduction compared with CT alone., Conclusion: PET for diagnosis and staging does not generate additional survival effectiveness compared with CT alone. However cost savings associated with its use and the improvement of therapeutic management therefore justify its generalization in clinical practice.

Objectives: The aim of this study was to compare the longitudinal quality of life (QoL) between LV5FU2-irinotecan and LV5FU2 alone or LV5FU2-cisplatin in a randomized Phase II trial in patients with metastatic gastric adenocarcinoma., Methods: Among 134 eligible patients, QLQ-C30 scores were collected and described at each 2 monthly follow-up visit during 6 months. The frequencies of QLQ-C30 score improvement were calculated and mixed models for repeated measurements were applied with or without extreme poorest imputation for missing scores. The "survival" until definitive global health score (GHS) deterioration was estimated., Results: At the 3rd follow-up, patients with a stable or improved global health ranged from 11% in the LV5FU2-cisplatin arm to 18% in the LV5FU2-irinotecan arm. The irinotecan-based-therapy presented 14 to 15 scores with a better QoL. The time until definitive GHS deterioration was globally similar between treatment arms., Conclusion: This study highlights a better impact of LV5FU2-irinotecan and the interest of QoL assessment in phase II trials to complement the risk-benefit judgement.

Aim: To determine the most cost-effective strategy using PET for mediastinal staging of potentially operable non-small-cell lung cancer (NSCLC)., Methods: Four decision strategies based on French NSCLC work-up practices for the selection of potential surgical candidates were compared, comprising CT only, PET for negative CT, PET for all with anatomical CT, and CT and PET for all cases. The medical literature was surveyed to obtain values for all variables of interest. Costs were assessed with reimbursements from the French healthcare insurance for the year 1999. Expected cost and life expectancy were calculated for all possible outcomes of each strategy. Sensitivity analysis was performed to determine the effects of changing variables on the expected cost and life expectancy., Results: Compared with the CT only strategy, CT and PET for all resulted in a relative reduction of 70% of surgery for persons with mediastinal lymph node metastasis. PET for all with anatomical CT was shown to be a cost-effective alternative to the CT only, with life expectancy increased by 0.10 years and expected cost savings of 61 euros. This strategy was more favourable than PET for negative CT. Overall, sensitivity analyses showed the robustness of the results., Conclusion: The introduction of thoracic PET for NSCLC staging is potentially cost-effective in France. Further clinical investigation might help to validate this result.

Objectives: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000., Materials and Methods: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates., Results: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers., Conclusion: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Objectives: Population-based registries are the best way to draw a picture of the management of a disease. The purpose of this study was to analyse therapeutic modalities for rectal cancers in seven French areas in 1990 and 1995, before and just after a consensus conference devoted to this topic., Methods: A community-based series of 945 patients (402 in 1990, 543 in 1995) with rectal cancer was used to assess therapeutic modalities and stage at diagnosis., Results: Colonoscopy was performed in most of the cases (90% in 1990 and 1995). There was significant change between 1990 and 1995 in stage at diagnosis and cancer resection. The rate of continence-preserving operations was similar in 1990 and in 1995, as was the rate of adjuvant radiotherapy. There was a shift between 1990 and 1995 from postoperative radiotherapy to preoperative radiotherapy. There was an increase in the use of adjuvant chemotherapy., Conclusion: Changes in the management of rectal cancer in France over the past few years have concerned mainly resection rate, stage at diagnosis and adjuvant therapy. The recommendations of the consensus conference were followed only partly, in particular for adjuvant preoperative radiotherapy, which has not reached its full development, and adjuvant chemotherapy, which tends to be overprescribed, considering how little is known about its effectiveness.

Aim: Monitoring cancer incidence and time trends is essential for cancer research and health care planning. The aim of the study was to compare the incidence of gastrointestinal cancers in twelve administrative area in France to estimate the national cancer incidence during 2000 compared with the preceding 20 years., Methods: Incidence data was provided by cancer registries and mortality data by the French national medical research institute (INSERM). The two data sets were modeled separately over the period 1988-1997 using age-cohort models. The incidence/mortality ratio obtained from these models was applied to the mortality rates of an age-cohort model of the entire population., Results: The estimated number of new cases of gastrointestinal cancer was 61,465 in 2000. Colorectal cancer was the leading localization with 36,257 cases. The incidence of gastrointestinal cancers was slightly higher in northern than in southern area. Incidence of esophageal cancer was three times that of liver cancer. Variations in incidence were less marked for other localizations. The incidence of gastric and esophageal cancer in the male population decreased between 1980 and 2000, on average by slightly more than 2% per year. Incidence of other cancers increased. The number of new cases of colorectal cancer increased by 50%. The rise in the incidence of liver cancer was particularly striking, with an increase from 2000 incident cases in 1980 to nearly 6000 in 2000., Conclusion: For most localizations, incidence of gastrointestinal cancers displays few geographical differences in France, but there has been a striking change in incidence trends over the past 20 years.

Objectives: Clinical trials have demonstrated that fecal occult blood screening for colorectal cancer can significantly reduce mortality. However, to be deemed a priority from a public health policy perspective, any new program must prove itself to be cost-effective. The objective of this study was to assess the cost-effectiveness of screening for colorectal cancer using a fecal occult blood screening test, the Hemoccult-II, in a cohort of 100,000 asymptomatic individuals 50-74 years of age., Methods: A decision analysis model using a Markov approach simulates the trajectory of the cohort allocated either to screening or no screening over a 20-year period through several health states. Clinical and economic data used in the model came from the Burgundy trial, French population-based studies, and Registry data., Results: Modeling biennial screening versus the absence of screening over a 20-year period resulted in a 17.7 percent mortality reduction and a discounted incremental cost-effectiveness ratio of 3357 Euro per life-year gained among individuals 50-74 years of age. Sensitivity analyses performed on epidemiological and economic data showed the strong impact on the results of colonoscopy cost, of compliance to screening, and of specificity of the screening test., Conclusions: Cost-effectiveness estimates and sensitivity analyses suggest that biennial screening for colorectal cancer with fecal occult blood test could be recommended from the age of 50 until 74. Our findings support the attempts to introduce large-scale population screening programs.

Unlabelled: The aim of our study was to evaluate and compare in thyroid cancer patients the predictive value for disease progression of thyroglobulin (Tg) levels measured under thyroid-stimulating hormone (TSH) stimulation, in the postoperative period just before (131)I ablative therapy and at the time of control 6-12 mo later., Methods: Two-hundred twelve consecutive patients treated for a well-differentiated thyroid carcinoma (184 papillary, 28 follicular) with no initial distant metastases were retrospectively studied. All patients had a total or near-total thyroidectomy followed by ablation with 3.7 GBq (131)I. Tg levels were determined just before ablative therapy (Tg1) and 6-12 mo later (Tg2). Thresholds of 30 and 10 ng/mL were used for Tg1 and Tg2, respectively. Univariate and multivariate analyses were performed to assess the predictive value for disease progression of the 2 Tg determinations., Results: Thirty patients had a Tg1 level > 30 ng/mL. Six to 12 mo later, 30 patients had a Tg2 level > 10 ng/mL, 19 of whom had initially a Tg1 level > 30 ng/mL. Disease progression was reported in 20 patients (9%). Progression-free survival rates were significantly lower in patients with a low Tg1 or Tg2 level but the difference was more important with Tg2. With univariate analysis, 5 variables were significantly associated with disease progression: Tg2, Tg1, node invasion, extrathyroidal extension, and tumor size. With multivariate analysis, only Tg2 (odds ratio [OR] = 16.4; 95% confidence interval [95% CI] = 5.7-47.4; P < 0.001) and node invasion (OR = 2.7; 95% CI = 1.0-7.2; P = 0.04) had an independent prognostic value. When only initial parameters were considered, Tg1 and node invasion were the 2 independent prognostic factors. The OR decreased for Tg1 (OR = 10.1; 95% CI = 4.0-25.7; P < 0.001) but increased for node invasion (OR = 4.4; 95% CI = 1.7-11.2; P = 0.002)., Conclusion: Among all clinical and tumoral variables, lymph node invasion and serum Tg level are 2 important parameters to define the risk of disease progression. Although Tg2 appears more significant than Tg1, both Tg levels measured under TSH stimulation, in the postoperative period and a few months after ablative therapy, have a predictive value. In clinical practice, patients at risk can be selected as soon as the initial lymph node status and Tg1 level are known.

Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7-16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3-10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2-95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4-59.4) and technical salesmen (OR 8.6, 95% CI = 2.4-30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0-22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0-14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.

This paper describes the methods and initial validation of a cost-effectiveness model developed to simulate the breast cancer screening situation in France. The first screening pilot programmes were set up in France in 1989 to test the feasibility of a decentralized screening model based in a large number of existing non-dedicated radiology centres. The present cost-effectiveness model was built as a tool to help guide current policy discussions on the future of screening in France. This Markov model compares the costs and effects expected when a screening programme is offered to a given cohort of women to those expected in the absence of screening. The model was initially validated using current results from the Bas-Rhin screening programme and local cancer registry epidemiological data. Over a 20-year period, 315 274 women would attend for screening, of whom 12 491 would be recalled for further assessment. 4423 cancers would be detected, resulting in 637 deaths. Screening allows the detection of 106 additional cancer cases, thereby preventing 92 deaths, and saves 1522 life-years compared with a situation without screening. Breast cancer mortality is reduced by 12.6%, yielding a cost-effectiveness ratio of 137 000 FF per life-year saved. The results of initial analyses suggest that the model is capable of suitably assessing the impact of breast cancer screening in terms of costs and effects. Further scenario analyses are needed to understand the impact of screening policy changes on the costs and effectiveness of future screening programmes.

Hypothesis: The cause of breast cancer is linked to many macroscopic events, including benign breast disease. In this study we asked whether molecular changes could discriminate fibroadenoma, which is one of the most common benign breast disease lesions associated or not with breast cancer., Design: Retrospective cohort study., Setting: Anticancer medical center., Subjects: Archival tissues in 32 cases of fibroadenoma, diagnosed in the same breast as a breast carcinoma, are compared with a control group of 26 cases of fibroadenomas unaffected by breast cancer., Main Outcome Measures: Histological features are characterized in all samples. The epithelial and stromal components are analyzed for a loss of heterozygosity and a microsatellite instability using a polymerase chain reaction-based method with 11 polymorphic microsatellite markers at 7 chromosomal regions frequently altered in breast cancer. The p53 gene mutations were also determined at exons 5 to 9., Results: The frequency of complex fibroadenomas was similar in both groups (P =.42). Only in the case group did we observe proliferative lesions confined in fibroadenomas, including atypical ductal hyperplasia (2 cases), lobular neoplasia (3 cases), or low-grade ductal carcinoma in situ (2 cases). There is no significant morphological difference between the 2 groups. Neither microsatellite alterations nor p53 gene mutations are present in the fibroadenoma components. Loss of heterozygosity is found only in the epithelial component of the 2 ductal carcinomas in situ confined in fibroadenomas., Conclusions: Genetic alterations, which are most frequently involved in malignant breast carcinomas, are not present in fibroadenomas, regardless of their association with breast cancer or their histological complexity. These findings suggest that fibroadenomas are not associated with breast carcinogenesis.

Mycosis fungoides (MF) is a rare disease with an unknown aetiology, although it has been suggested that infections may play a role. The present study investigates whether infections, atopic disorders and some other diseases are risk indicators for MF. A European multicentre case-control study involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n = 140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible; 22 cases were not accepted. Of the 118 accepted cases, 104 patients were interviewed (including 76 definitive cases and 28 possible cases). These 76 definitive cases were used for this study. A common set of controls to serve all case groups were interviewed, representing a total of 4574 controls. The latter included 1008 colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country. The highest ORs for MF were found in patients who reported a history of psoriasis 5 years before MF was diagnosed (OR 7.2, 95% CI: 3.6-14.5). Urticaria had an OR of 1.4 (95% CI: 0.6-3.6). Infections and atopic diseases were not closely associated with MF. Some diseases correlated to MF. Whether this has a causal background or reflects early diagnostic uncertainty is not known.

Mathematical models have been shown to be useful in predicting the cost-effectiveness of cancer screening programmes. We designed a computer macro-simulation model aimed at predicting the cost-effectiveness of alternative colorectal cancer screening strategies. This model was built to determine the cost-effectiveness of a biennial screening programme using the Hemoccult test in Burgundy (France). It was validated with data from the Danish randomized study. Estimates of our model showed an extremely close concordance with observed results in the Danish study. The observed mortality reduction was 18.0% and the estimated mortality reduction was 18.4%. Preliminary data from the Burgundy study predict a 14.6% colorectal cancer mortality reduction after 10 years. Sensitivity analyses were performed with different assumptions regarding the participation rates and the lead-time. This model can serve to assess the cost-effectiveness of a variety of screening modalities.

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.

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.

Background: Colorectal cancer prevalence is an important determinant of the health demand that completes information provided by cancer incidence. Current estimations established from data for the years 1985 and 1995 can be used to establish a precise description of changing healthcare needs for colorectal cancer., Method: Prevalence estimates method were based on incidence data computed on the regional scale by the FRANCIM network and mortality data provided by INSERM. We used the relationship that exists between the net risk of cancer, the net risk of dying of the given cancer and the age-specific prevalence of cancer., Results: In 1995, the prevalence of patients who had a diagnosis of colorectal cancer amounted to 200 000 persons. The estimated number of prevalent cases was never lower than 3500 in any region and in 7 regions this number was higher than 10 000. From 1985 to 1995, there has been an increase of 35% in the prevalence rates., Conclusion: The evaluation of the number of persons who have had a diagnosis of colorectal cancer provides knowledge for health care planning. Such information on the regional scale is very useful for the health organisation (SROS). This geographical level induces difficulties not encountered at the national level.

With 10,882 estimated new cases in 1995 in France, lip, oral cavity and pharynx tumours rank 4th, representing 8.1% of all cancers in men. They are less frequent in women, with a sex ratio of 7. Based on the French cancer registries data which cover 13% of the metropolitan territory in 2000, both incidence and mortality increased until early 1980s to decrease thereafter. The main hypothesis proposed to explain the French leadership world-wide for these tumours deals with alcohol and tobacco consumption. Important differences observed between several areas within Europe, for some subsites, in connection with age or sex, are pointing toward the need of new studies about environment and/or genetics. Until now, comparisons between countries were made at the level of lip, oral cavity and pharynx category as a whole or by large subgroups. In this work we attempt to establish more accurate statistics, in order to comply with the situation of this cancer in France. Present results should encourage the scientific community to conduct site specific epidemiological studies.

Purpose: A retrospective study to demonstrate the safety of corneas from donors affected by systemic malignancies in a view of keratoplasty., Methods: Using the data of the cancer registry department in a district of 500,000 residents, we analyzed retrospectively 143 patients followed up in the same region and transplanted between 1987 and 1995. We compared the incidence of cancer in recipients of cornea coming from donors with malignancies with recipients of cornea from donors without malignancies. The rate of cancer in this population was also compared with the incidence of cancer in the general population at the same age., Results: Eleven patients (7%) were excluded from the study, eight of them for the presence of cancer in their medical history before surgery and the three others because of lack of information about their follow-up after surgery. Forty patients received corneas from cancerous donors and 103 from donors without cancer. Six patients developed malignancies between 1 and 4 years after transplantation, and only one of them received a cornea from a donor with a systemic malignancy. This recipient developed a different type of cancer from that of the donor. The five other patients received corneas from donors without systemic malignancies. By comparing theses results, there was no relationship between the occurrence of malignancies and transplantation of corneas from cancerous donors (relative risk = 0.49, 95% confidence interval = 0.01-13.62)., Conclusion: There was no increased incidence of cancer in our patient population compared with reference population. Based on this study, there is no statistical or clinical evidence to suggest the transmission of cancer from donors with malignancies via corneal transplantation, according to the accepted criteria of donor selection.

Background: One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended., Objectives: To evaluate the relevance of this risk in routine clinical practice., Methods: Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment., Results: Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure., Conclusions: Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.

A cost-effectiveness analysis was carried out from a randomized placebo-controlled protocol of GM-CSF during and after remission induction treatment for elderly patients with acute myeloid leukemia (AML). A retrospective economic analysis was carried out from the hospital perspective. A total of 240 patients with de novo AML and aged 55 to 75 years were enrolled. Overall survival and disease-free survival were analysed for efficacy within five years and expressed in gained life-years. Analysis was also conducted according to the protocol stratification: 55-64-year-old and 65-75-year-old patients. Global costs were estimated on the basis of patient medical records from inclusion to death or relapse. In all, 83 patients were evaluated from three centres, Besançon, Nancy and Nantes. Costs are expressed in French francs. Overall, total cost per patient amounted to FF 641,778 for placebo patients and to FF 587,048 for GM-CSF patients. For disease free-survival, costs were FF 357,167 for placebo patients and FF 320,736 for GM-CSF patients. For overall survival and disease free-survival the cost savings by GM-CSF were, respectively, FF 54,730 and FF 36,431. In the younger patient group savings were synonymous with GM-CSF. In all cases GM-CSF strategy induced benefit expressed as savings as well as efficacy.

The incidence of mycosis fungoides (MF) is low, and the aetiology of the disease is unknown. The aim of this study was to investigate whether wine consumption protects against the disease and whether smoking constitutes a risk factor. This paper is part of the European Rare Cancers Study that tries to determine the risk factors for seven selective rare cancers, including mycosis fungoides, involved in the development of cancer. A multicentre case-control study was conducted in six European countries. Only incident cases with confirmed histology were included in the analysis which include a total of 76 cases of MF and 2899 controls. Wine intake had no protective effect; on the contrary the consumption of more than 24 g of alcohol per day was associated with a high risk of MF (odds ratio (OR)=3.02, 95% confidence interval (CI), 1.34-6.79), after adjusting for centre, country, age, sex and education. There was a dose-dependent increase in the risk of MF with increased smoking habits, albeit the observed trend was not statistically significant. A combined exposure to high tobacco and alcohol use yielded a significantly increased risk factor for MF (P=0.0073). Alcohol intake was associated with MF.

OBJECTIVE: Intravascular ultrasound (IVUS) can be used to optimize the deployment of stents. The aim of this study was to assess the acute and long-term medical costs of the use of IVUS through the results of the 'REStenosis after Intravascular ultrasound STenting' (RESIST) study. METHODS: One hundred and fifty-five patients were randomized to routine stent deployment with (n = 79) versus without (n = 76) IVUS guidance, with clinical follow-up over 18 months. The medical costs (hospitalization plus procedural costs) were calculated using a cost accounting system at the time of stent implantation and for all repeat lesion revascularizations. (At the time of writing the exchange rate was 1 Euro = 1 US dollar.) RESULTS: Because of the cost of IVUS catheters and the need for more balloons, acute procedural costs were 18% higher in the group with IVUS guidance (2934 +/- 670 Euros vs 2481 +/- 911 Euros). Clinical events (death, myocardial infarction, unstable angina or lesion revascularization) occurred in 28/76 (37%) in the group without IVUS, versus 20/79 (25%) (OR = 1.7; 95%CI = [0.82; 3.63]) in the group with IVUS. There was a higher number of revascularization procedures in the control group (31 in the control group vs 20 in the IVUS group). The cumulative medical costs at 18 months were only slightly higher in the IVUS group (4535 +/- 2020 Euros vs 4679 +/- 1471 Euros in the IVUS group), as the higher acute costs in the group with IVUS guidance were partially offset by the lower cost for revascularization procedures. Sensitivity analysis using variations of the unit costs as well as variations in the number of revascularization procedures and length of hospital stay showed that the overcost remained in a range between 1% and 7.6%. CONCLUSIONS: Over 18 months of followup, despite higher acute costs, IVUS optimization of stent deployment did not considerably increase the medical costs.

Overall evidence from epidemiologic studies in the workplace suggests that dioxin is a human carcinogen, but whether low doses affect the general population remains to be determined. The authors examined the spatial distribution of soft-tissue sarcomas and non-Hodgkin's lymphomas around a French municipal solid waste incinerator with high emission levels of dioxin (16.3 ng international toxic equivalency factor/m3). Not consistently associated with dioxin exposure,-Hodgkin's disease served as the control cancer category. Clusters were identified from 1980 to 1995 in the area ("département') of Doubs by applying a spatial scan statistic to 26 electoral wards. The most likely and highly significant clusters found were identical for soft-tissue sarcomas and non-Hodgkin's lymphomas and included the area around the municipal solid waste incinerator; standardized incidence ratios were 1.44 (observed number of cases = 45, focused test p value = 0.004) and 1.27 (observed number of cases = 286, focused test p value = 0.00003), respectively. Conversely, Hodgkin's disease exhibited no specific spatial distribution. Confounding by socioeconomic status, urbanization, or patterns of medical referral seemed unlikely to explain the clusters. Although consistent, these findings should be confirmed by further investigation (e.g., a case-control study in which dioxins are measured in biologic tissues) before clusters of soft-tissue sarcoma and non-Hodgkin's lymphoma are ascribed to dioxin released by the municipal solid waste incinerator.

Concept: Quality of life assessment in cardiology has become an important point in the overall evaluation of anticancer treatments. Quality of life is a multidimensional subjective concept usually assessed by self-administered questionnaires with a linear analogous design. Multiple choice questions can also be used to explore several dimensions of quality of life., Questionnaires: No one questionnaire is ideal. Two appear to be most widely used worldwide. The main body of these modular questionnaires is completed by specific sections dealing as needed with designated organs or treatment toxicity. Data interpretation is particularly difficult and must take into consideration the fact that most currently used questionnaires measure health in general rather than the philosophical concept of quality of life., Clinical Application: Use of quality of life questionnaires varies greatly. These tools can be used to estimate the impact of public health measures or treatments in general. They are most widely used to date as assessment tools for therapeutic trials or to provide secondary criteria in trials where survival is the main outcome criteria. In this case, they provide a means of comparing symptomatic treatment and anticancer treatments or two different anticancer treatments. Studies are under way to use quality of life scales in everyday patient care., Perspectives: Certain authors have attempted to combine quality and quantity of life in a single tool in order to obtain a global index which could be used to compare large groups of patients. Different tools are still in the development phase.

Objectives: The objective of this work was to study the reporting of resected colonic carcinomas and to compare them with Consensus Guidelines published in January 1998., Methods: The study included 535 colonic carcinomas collected in 8 French registries in 1995, and chosen by drawing lots. For each report, the presence of the information requested by the Guidelines was looked for. Three synthetic variables were built: 2 scores and one qualitative at 2 classes. The influence of patients, tumour and health care system's characteristics was analysed on the 3 dependent variables., Results: Some important variations were observed for information's percents in reporting. In monovariate analysis, scores were significantly influenced by cancer's sub-location, area of patient's residence, surgical center, type of laboratories and pathologist case volume. In multivariate analysis, significant heterogeneity in practices remained between geographical areas. Types of laboratories and pathologist case volume affected differently dependent variables., Conclusion: This study shows the necessity to assess the practices before consensus because of the impact of pathological forms in therapeutic decisions and variations observed.