Quantifier l’effet des récidives multiples au cours du temps sur le risque de progression dans une large cohorte de patients atteints d’un cancer de vessie superficiel de bas grade TaG1, et évaluer les facteurs pronostiques de récidives multiples, en prenant en compte les événements répétés. Nous avons analysé rétrospectivement une cohorte française de 470 patients nouvellement diagnostiqués pour carcinome urothélial de vessie TaG1 entre 1986 et 2010 et suivis jusqu’en 2012. L’association entre le nombre de récidives et le risque de progression non invasive (TVNIM) et progression invasive (TVIM) a été évaluée avec un modèle de Cox à variable dépendante du temps et par une analyse de landmark pour prendre en compte la survenue d’événements au cours du suivi. Les caractéristiques des récidives, comme le temps d’occurrence ou la localisation, et le risque de nouvelles récidives ont étés évalués avec des modèles à fragilité adaptés à la corrélation intra-patient induite par les évènements récurrents. Parmi les 470 patients TaG1 analysés, un total de 251 patients ont récidivé, 34 ont eu au moins une progression TVNIM et 17 une progression TVIM. Le suivi médian était de 7,20 ans (intervalle interquartile : 4,20–10,88 années). Aucune association entre le nombre de récidives et le risque de progression n’a été mise en évidence mais un antécédent de deux récidives ou plus était associé à un hazard ratio de 4,7 du risque de récidives ultérieures. De même, un temps d’occurrence entre deux récidives inférieur à six mois et une localisation multifocale augmentaient le risque de récidives ultérieures. La corrélation intra-patient mesurée par la variance de l’effet aléatoire, dit de fragilité, était faible laissant à supposer que les événements répétés étaient relativement indépendant les uns des autres. Une étude de sensibilité de l’association entre caractéristiques des récidives et risque de récidives ultérieures selon le temps de landmark a renforcée cette hypothèse d’indépendance des récidives. Le nombre de récidives TaG1 ne semblait pas être un facteur pronostique fort de progression, mais augmentait significativement le risque de nouvelles récidives. Un court délai (< 6 mois) entre deux récidives consécutives et une localisation multifocale étaient des facteurs pronostiques de nouvelles récidives. Ces caractéristiques sont facilement identifiables et à bas coût. Leur utilisation pour adapter le rythme de surveillance pourrait être testée en routine clinique. Les extensions du modèle de Cox avec des variables dépendantes du temps, des analyses de landmark et les modèles à fragilité offrent des outils puissants pour étudier l’occurrence d’événements survenant au cours du suivi.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

We present a new statistical model for the analysis of case‐control or cohort studies examining a highly polymorphic candidate disease susceptibility gene. Many genotypes are possible for such a gene. Consequently, the average number of subjects having each genotype will be modest. If analyzed separately, the risks associated with most genotypes will be estimated imprecisely. Our Bayesian partition model clusters genotypes according to risk, only allowing partitions that satisfy a particular assumption about the joint effect of the two alleles making up a genotype. This assumption is genetically plausible, imposes structure on the set of genotype risks, and still leaves a highly flexible model. By Bayesian model averaging over partitions, the model becomes, in effect, a semiparametric model for genotype risk. It allows borrowing of strength, i.e., estimates of risk for one genotype are informed by the risk estimates of all the genotypes. We present the results of fitting the model to two datasets, one simulated and one genuine case‐control study of the NAT1 gene and lung cancer, and compare it in a simulation study with a haplotype relative risk model. The partition model enables genotype risks to be estimated more accurately and the alleles to be ranked according to risk. Genet. Epidemiol. 22:356–368, 2002. © 2002 Wiley‐Liss, Inc.

BACKGROUND Prophylactic cranial irradiation (PCI) has a beneficial effect on overall survival in patients with small-cell lung cancer (SCLC) in complete remission as shown in a worldwide meta-analysis. The current analysis aimed to evaluate PCI effects on patterns of failure in this patient category. PATIENTS AND METHODS The Institut Gustave-Roussy coordinated two parallel randomized studies including a total of 511 patients with SCLC. Patients were randomly assigned to either PCI (24 Gy in eight fractions and 12 days) or no PCI. Patterns of failure were analyzed according to (i) total event rates and (ii) isolated first site of relapse using a competing risk approach. RESULTS Five hundred and five patients were analyzed. The 5-year cumulative rate of brain metastasis as an isolated first site of relapse was 37% in the control group and 20% in the PCI group (P < 0.001). The overall 5-year rates of brain metastasis were 59% and 43%, respectively [relative risk (RR) 0.50; P < 0.001]. The 5-year overall survival rates were 15% in the control group and 18% in the PCI group (RR 0.84; P = 0.06). CONCLUSIONS PCI decreased significantly the risk of brain metastasis. Other events were not influenced. The relative death risk reduction was of borderline significance. Results reported as isolated first cause of failure and subsequent competing events may explain why a major treatment effect on brain metastases rate has a rather moderate effect on survival.

Since the late 1960s, the prevalence of smoking among European women has sharply increased, and lung cancer rates in women have recently shown a parallel increase. Rates among young women are now nearly equal between men and women in the Scandinavian countries.1 In many developed countries, prevalence of tobacco smoking is now higher in young women than in young men.2 Although previous studies have identified tobacco smoking as an important risk factor of lung cancer among young women,3, 4 the rarity of lung cancer in this group hampered a detailed assessment of the quantitative aspects of tobacco smoking, in particular among women aged less than 40 or even less than 35. Within the frame of a pooled analysis of case-control studies of tobacco smoking and lung cancer conducted in Western Europe between 1991 and 1994, we identified 116 female cases of lung cancer and 175 age-matched controls under the age of 45. These subjects were recruited from 2 centres in Germany (46 cases and 43 controls), 1 in Spain (14 and 27) and one in France (56 and 105). Detailed information was collected on the history of tobacco smoking. Control subjects were selected from patients admitted to the same hospitals as the cases for disease not related to tobacco smoking (in Spain and France) or from a random sample of residents of the study areas (in Germany). The cases and controls from the German centres were included in previous analyses.4, 5 We calculated the odds ratios of lung cancer and their 95% confidence intervals (CIs) based on multivariate logistic regression, after adjusting for centre and single year of age, and stratifying by 5-year age groups. Among women aged less than 40 and in particular among those aged less than 35, the carcinogenic effect of tobacco smoking, albeit present, was weaker than among those aged 40 or more (Table I). This pattern held true for ever-smokers, current smokers and ex-smokers, and across categories of comparable duration of smoking, cumulative tobacco consumption and average daily consumption of cigarettes. None of the differences in results among age-groups, however, was statistically significant; for example, the p-value of interaction terms between age-group and cumulative consumption were 0.5 (<35 vs. 35–39) and 0.25 (35–39 vs. 40–44). Cases with small cell carcinoma represented 34% of total cases, whereas adenocarcinoma and squamous cell carcinoma comprised 23% and 12% of total cases: the distribution by histological type was similar in the 3 age groups shown in the table. The fraction of lung cancer cases attributable to ever smoking was 0.54 (95% CI 0.11–0.97) among women below age 35, 0.58 (95% CI 0.26–0.90) among women aged 35–39, and 0.84 (95% CI 0.72–0.96) among women aged 40–44. Our results suggest a smaller role of tobacco smoking in lung carcinogenesis in very young women as compared to other women, that is not explained by a lower consumption of tobacco in the former group. The difference might be due to the fact that latency in very young women was inadequate to completely observe the carcinogenic effect of tobacco smoking. Alternatively, defence mechanisms against tobacco carcinogens might be stronger during early adulthood as compared to later in life. A different role of genetic susceptibility could also be involved, as suggested also by the higher proportion of never smokers among cases in the young age groups (4/15, 8/35 and 6/66 respectively). Given the long latency of the carcinogenic action of tobacco smoke, however, our results do not support the notion that smoking tobacco early in life poses a lower long-term carcinogenic risk than smoking later in life.

Objective: We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case–control study.

To know if included patients in a study are alive or dead is essential. In practice, the knowledge of vital status is a pre-requisite to the collection of the medical cause of death in epidemiology. In clinical research all investigators, particularly those in cancerology, must recuperate this information for all patients lost to follow-up. There are two methods to obtain the vital status of a subject: to have access to the civil status register of the local town hall where the subject was born, or to contact the "Institut National de la Statistique et des Etudes Economiques" (INSEE). We describe each of these procedures: ways to put them into practice, their efficacy and problems encountered. To write to town halls is a simple efficient method and is advised when the number of sujects is small, but this procedure poses a problem of confidentiality. The examination of the tapes of registered deaths from INSEE is recommended for many querries concerning a lot of subjects.

To know if included patients in a study are alive or dead is essential. In practice, the knowledge of vital status is a pre-requisite to the collection of the medical cause of death in epidemiology. In clinical research all investigators, particularly those in cancerology, must recuperate this information for all patients lost to follow-up. There are two methods to obtain the viral status of a subject: to have access to the civil status register of the local town hall where the subject was born or to contact the "lnstitut National de la Statistique et des Etudes Economiques" (INSEE). We describe each of these procedures: ways to put them into practice, their efficacy and problems encountered. To write to town halls is a simple efficient method and is advised when the number of sujects is small, bat this procedure poses a problem of confidentiality. The examination of the tapes of registered deaths from INSEE is recommended for many querries concerning a lot of subjects.

Tobacco is responsible for 80 to 90% lung cancer cases in industrialized countries. However, genetic factors are likely to be involved in lung cancer susceptibility. Some degree of familial aggregation of lung cancer is evidenced in most family studies. On the other hand, many tobacco carcinogens are metabolised by enzymes of the P450 cytochrome family. Two enzymes of cytochrome 450, CYP1A1 and CYP1A2, are inducible by tobacco carcinogens, and animal studies evidenced a genetic polymorphism of CYP1A1 associated with tumour occurrence after administration of a polycyclic aromatic hydrocarbone. In humans, an association between lung cancer and some P450 polymorphisms (CYP1A1, CYP2D6, CYP2E1) was suggested but the results of epidemiologic studies are discordant and difficult to interpret. In addition, there is a polymorphism of glutathion S-transferase isoenzyme (GSTM1) involved in carcinogen elimination; an association between this polymorphism and lung cancel has also been reported. Further studies on combined effects of these polymorphisms should allow an identification of sub-groups of individuals at high risk of lung cancer.

A case-control study of 196 histologically proved cases of renal cell carcinoma and 347 controls matched for age at interview, sex, hospital, and interviewer was conducted in France between 1987 and 1991. A complete occupational history was recorded for each patient and occupations were coded blindly according to the International Standard Classification of Occupations. In women, none of the risks were significant. Among men, after adjustment for the educational level, cigarette smoking, and Quetelet index before diagnosis, significantly increased matched odds ratios (ORs) were found for sales workers (OR = 2.1, 95% confidence interval (95% CI) 1.2-4.0), managers (OR = 3.3, 95% CI 1.2-8.9), and textile workers and tailors (OR = 6.2, 95% CI 1.1-33.7). For this last occupational group, an increase in risk was found with an increased duration of exposure.

BACKGROUND:To date, the effect of tar exposure, the use of a filter and the type of tobacco (light or dark) on the risk of lung cancer have not been studied together.METHODS:Data from a case-control study on lung cancer were used to evaluate the specific effects of these three parameters. Cases of lung cancer and controls were interviewed in hospitals in France from 1976 to 1980. The past tar content of cigarettes distributed by the French Tobacco Monopoly was obtained. The results presented concern an exclusively male population of lifelong smokers of French cigarettes and lifelong smokers of light imported cigarettes. The population comprised 1114 cases of histologically confirmed lung cancer and 1466 hospitalized controls.RESULTS:An increase in risk was found among smokers of both dark and light cigarettes (relative risk [RR] = 2.6, 95% confidence interval [CI]:1.1-6.5) and among lifelong smokers of dark cigarettes (RR = 1.7, 95% Cl: 0.9-3.2) compared to lifelong smokers of light cigarettes. Similarly, the risk of lung cancer was higher among smokers of both non-filter and filter cigarettes (RR = 1.6, 95% Cl: 0.9-2.7) and among lifelong smokers of non-filter cigarettes (RR = 1.6, 95% Cl: 0.9-2.8) than among lifelong smokers of filter cigarettes. A borderline significant increase in risk was observed for smokers of French cigarettes compared to smokers of light imported cigarettes (RR = 2.6, 95% Cl: 0.9-7.7). No significant difference in the risk of lung cancer was observed among smokers of French cigarettes according to the proportion of years of smoking high tar cigarettes.CONCLUSION:This study tends to demonstrate a separate effect of type of tobacco, use of a filter and tar content in addition to the usual characteristics of cigarette smoking on lung cancer risk.

A hospital‐based case‐control study of renal‐cell carcinoma was conducted in France from 1987 to 1991. A total of 196 histologically confirmed cases (138 males and 58 females) and 347 controls (235 males and 112 females), matched for sex, age at interview, hospital and interviewer, were included. The risk of renal‐cell carcinoma was not apparently increased with number of cigarettes per day, duration of smoking or early age at first cigarette smoking in males. No significant trend was found in the risks with increasing Quetelet index (Ql) at the age of 20 in males. On the contrary, the risks increased significantly with an increasing Ql prior to diagnosis. In females, the trends in risks were significant both for the relative weight at the age of 20 and prior to diagnosis. The consumption of regular or decaffeinated coffee, tea or alcoholic beverages was not associated with renal‐cell carcinoma, in males or in females. © 1993 Wiley‐Liss, Inc.

A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture, of nicotine gum and the effect of the association on smoking cessation. After a one-year follow-up period, the success rates were in the same order of magnitude for nicotine gum (active treatment: 10%, placebo: 8%) group and for acupuncture (active treatment: 8%, placebo: 10%) group.

Between 1970 and April 1982, 592 women with T1, small T2, N0, N1, M0 breast cancer were managed by lumpectomy, axillary dissection and radiotherapy at the institut Gustave-Roussy (IGR). The overall cosmetic result and the degree of asymmetry, fibrosis and telangiectasia of the treated breast were assessed by the radiation oncologist at each follow-up visit. The changes in these cosmetic parameters with time are shown. At 5 years the overall cosmetic result was excellent in 58%, good in 38% and fair or poor in 8%. A multivariate analysis was performed of the factors associated with a cosmetic defect. The most significant factors were tumour size, the presence of defect after surgery and the daily applied dose per fraction to the breast. Surgical and radiotherapy technique (especially alternate day fractionation) can significantly affect the cosmetic result obtained.