Water resources variability in Africa during the 20th century = Variabilité des ressources en eau en Afrique au 20ème siècle

Dans ce travail, on étudie les phénomènes ondulatoires d'échelle synoptique en Afrique de l'Ouest à l'aide des réanalyses du NCEP/NCAR de 1979 à 1995. Une analyse spectrale sur cette période nous montre qu'il existe régulièrement et distinctement dans le vent méridien à 700 hPa une périodocité entre 3 et 5 jours et une autre entre 6 et 9 jours. Un filtrage numérique est alors effectué pour isoler ces deux phénomènes ainsi qu'une analyse composite afin de cerner les structures moyennes des ondes associées. Ensuite, aux dates de passage de ces perturbations, nous essayons de voir comment certaines variables liées à la convection sont modulées. L'onde 6-9 jours semble être un autre régime d'onde d'Est avec une cinématique différente de celle de l'onde 3-5 jours. Elle est caractérisée par son intermittence. Par ailleurs, nous avons trouvé des interactions différentes entre ces deux perturbations et les précipitations observées par l'ORSTOM. (Résumé d'auteur

Le taux préopératoire d’IL-6 sérique comme marqueur prédictif d’atteinte médiastinale dans le cancer bronchique non à petites cellules de stage Ic

Session ThoraciqueObjectif : Le cancer bronchique non à petites cellules (CBNPC) est la première cause de mortalité par cancer dans le monde. Son pronostic dépend de son stade TNM. Une atteinte ganglionnaire médiastinale est un critère de mauvais pronostic et les patients cN2 ne tirent que rarement bénéfice d’une exérèse chirurgicale. Le but de cette étude était d’évaluer la pertinence de marqueurs biologiques qui pourraient traduire l’agressivité tumorale.Méthode : Nous avons effectué une étude monocentrique prospective sur 42 patients cT1N0 qui ont bénéficié d’une lobectomie avec curage ganglionnaire médiastinal radical entre mai 2001 et juillet 2003 pour CBNPC. Avant l’intervention, nous avons dosé 4 cytokines dans le sang : IL-6, IL-10, TGFB et VEGF. Le stade clinique était évalué par scanner thoracique injecté, le TEP-scanner n’était pas disponible en routine. Nous avons comparé ces taux de cytokines à ceux de 38 sujets contrôles.Résultat : Le taux d’IL-6 sérique était significativement plus élevé dans le groupe des opérés comparés aux sujets sains (33,45 ± 92,9 pg/ml vs 2,10 ± 3,2 pg/ml, p 9 pg/ml (p = 0,0039) et la lymphopénie (p = 0,026). En analyse multivariée, le taux d’IL-6 était un facteur pronostic indépendant (p = 0,0063, HR = 3,7 [1,45-9,44]). Ce taux d’IL-6 n’était pas corrélé à la taille de la tumeur (p = 0,98), mais clairement associé à l’atteinte ganglionnaire (p = 0,002).Conclusion : L’IL-6 est une cytokine pléiotrope impliquée dans la réponse immunitaire, l’angiogenèse et l’inflammation. Elle est connue comme étant un marqueur d’agressivité tumorale dans certaines hémopathies malignes ou d’autres cancers solides. Nos résultats suggèrent clairement que le taux d’IL-6 peut être considéré comme un marqueur d’atteinte ganglionnaire dans les stades précoces de CBNPC indépendamment de la taille tumorale. La corrélation de ce taux d’IL-6 au TEP-scanner doit être évaluée

Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma

Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting. In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK-or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation. Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3. In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed. Abbreviations: ALK = anaplastic lymphoma kinase, ECOG PS = the Eastern Cooperative Oncology Group performance status, EGFR = epidermal growth-factor receptor, GFPC = French Lung Cancer Group, HR = hazard ratio, ICI = immune-checkpoint inhibitor, NSCLC = non-small-cell lung cancer, OS = overall survival, PFS = progression-free survival, ROS-1 = c-ros oncogene 1, TKIs = tyrosine-kinase inhibitors

Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01.

International audiencePURPOSE: This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer (SCLC). PATIENTS AND METHODS: One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4'-epidoxorubicin (PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide (400 mg daily) or placebo. RESULTS: After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo (n = 43) or thalidomide (n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant (minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log-rank test: hazard ratio [HR] = 0.74; 95% CI, 0.49 to 1.12; P = .16). Patients with a performance status (PS) of 1 or 2 who received thalidomide had a significantly longer survival (HR = 0.59; 95% CI, 0.37 to 0.92; P = .02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide (HR = 0.54; 95% CI, 0.36 to 0.87; P = .02), whereas the difference did not reach statistical significance for the whole population (HR = 0.74; 95% CI, 0.49 to 1.12; P = .15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group (33% v 12%, respectively). CONCLUSION: Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 (exploratory analyses), deserving further studies targeting angiogenesis in this disease

Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors

International audienceThe prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor

Telomere Status of Advanced Non-Small-Cell Lung Cancer Offers a Novel Promising Prognostic and Predictive Biomarker

Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of TERT and shelterin complex genes (TRF1, TRF2, POT1, TPP1, RAP1, and TIN2), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low RAP1 expression (p = 0.0035 and p = 0.0069), and tended to show higher TERT levels (p = 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS, p = 0.0023) and overall survival (OS, p = 0.00041). TERT and TRF2 overexpression correlated with poor EFS (p = 0.0069 and p = 0.00041) and OS (p = 0.0051 and p = 0.007). Low RAP1 and TIN2 expression-levels were linked to reduced EFS (p = 0.00032 and p = 0.0069) and OS (p = 0.000051 and p = 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (p = 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment

Telomere Status of Advanced Non-Small-Cell Lung Cancer Offers a Novel Promising Prognostic and Predictive Biomarker

Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of TERT and shelterin complex genes (TRF1, TRF2, POT1, TPP1, RAP1, and TIN2), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low RAP1 expression (p = 0.0035 and p = 0.0069), and tended to show higher TERT levels (p = 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS, p = 0.0023) and overall survival (OS, p = 0.00041). TERT and TRF2 overexpression correlated with poor EFS (p = 0.0069 and p = 0.00041) and OS (p = 0.0051 and p = 0.007). Low RAP1 and TIN2 expression-levels were linked to reduced EFS (p = 0.00032 and p = 0.0069) and OS (p = 0.000051 and p = 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (p = 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment