Search

Benefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen.Eligibility criteria: age 18-70 years, ECOG PS 0-1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival.Between 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected.Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome.NCT01631136.

International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.

Background Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. Methods All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. Results Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age > 14 vs. 40% and 41% for 12–14 and ≤ 12 years, respectively; P = 0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P = 0.048), and by 9% for each year at age at first birth (P = 0.035). ALK alteration frequency was greater in women with high parity (50% in ≥ 5 vs. 12% and 7% for 1–4 and nulliparity, respectively; P = 0.021). Conclusion In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Purpose Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non–small-cell lung cancer (nsNSCLC). Methods In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671 . Results One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44–0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8–30·3) and 5·5% (95% CI: 0·0–11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group). Conclusion Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. Clinical trials registration number ClinicalTrials.gov Identifier: NCT01763671 .

Purpose: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell-lung cancer (nsNSCLC). Methods: In this multicentre, open-label phase 3 trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive paclitaxel 90 mg/m² (D1, D8, D15) plus bevacizumab 10 mg/kg (D1, D15) every 28 days or docetaxel (75 mg/m²) every 21 days; crossover was allowed after disease progression. Primary endpoint was progression-free survival (PFS). Results: Between May 2013 and August 2014, 166 patients were randomized (paclitaxel plus bevacizumab: 111, docetaxel: 55). Median PFS was longer in paclitaxel plus bevacizumab patients than in docetaxel patients [5·4 months vs 3·9 months, adjusted hazard ratio (HR) 0·61 (95% CI 0·44-0·86); p=0·005]. Objective response rates (ORR) were respectively 22·5% (95% CI 14·8-30·3) and 5·5% (95% CI 0·0-11·5) (p=0·006). Median overall survivals were similar (adjusted HR 1·17; p=0·50). Crossover occurred in 21/55 (38·2%) docetaxel-treated patients. Grade 3-4 adverse events were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p=NS), including neutropenia (19·3% vs 45·4%), neuropathy (8·3% vs 0·0%), and hypertension (7·3% vs 0·0%). Three patients died due to treatment-related adverse events (1·8% in each group). Conclusion: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared to docetaxel in nsNSCLC patients, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT01763671. Funding Statement: The study was sponsored by IFCT. Roche (Boulogne Billancourt, France) supplied bevacizumab, and a complementary grant but had no role in the study design, conduct of the study, and data analysis and had no other involvement in the study. The study was also supported by the French National Cancer Institute (INCa) and French League Against Cancer. Declaration of Interests: ABC has received honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Pfizer, and travel grants from Roche, AstraZeneca, Boehringer Ingelheim, Novartis and Pfizer. CAV has declared grants, personal fees and non-financial support from Roche. OM has declared personal fees from BMS, Boehringer Ingelheim, Astra Zeneca, Novartis, ans Hoffman-Roche. FB has declared personal fees from Astra Zeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. GZ has declared grant from Roche and BMS, personal fees from Roche, BMS, Astra Zeneca, and MSD, and non-financial support from BMS, Astra Zeneca and Pfizer. DP has declared has declared personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. CFD has declared other from MSD (CPLF 2017), Laidet Medical (ERS 2016), and Boehringer Ingelheim (CPLF 2016). EP has declared personal fees and non-financial support from Astra Zeneca, BMS and personal fees from Pfizer. DMS has declared personal fees from Roche, BMS, MSD and Eli Lilly. BB has received institutional grants for clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, OncoMed, Inivata, OSE Pharma. Ethics Approval Statement: This study was approved by a local Ethic Committee (CPP Nord-Ouest III, France), and complied with French legislation, Good Clinical Practices, and the principles outlined in the latest version of Declaration of Helsinki. After approvals, the study was implemented in 36 hospitals and cancer centres in France.

Introduction This single-arm phase II trial aimed to evaluate a stop-and-go strategy with cisplatin-based chemotherapy and bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC). Methods Patients were initially treated with three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 1) followed by bevacizumab maintenance and after progression, re-introduction of three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 2) and pemetrexed plus bevacizumab maintenance. The primary endpoint was the proportion of patients with advanced non-squamous NSCLC receiving the complete sequence 2 without platinum dose reduction (hypothesis ≥75%). Results 120 patients with performance status ≤1 were included. Of 113 patients evaluable for efficacy, 65 (57.5%) entered in sequence 2 and 56 (86%) received the three planned cycles including 37 (56.9%, 95% CI 45.1 to 73.6) without platinum dose reduction. The median progression-free survival 1 (PFS1; inclusion to progression 1) was 5.6 months (95% CI 5.0 to 6.3) and median PFS2 (progression 1 to progression 2) was 6.8 months (95% CI 5.8 to 8.8). The median disease control duration (PFS1+PFS2; n=65) was 12.4 months (95% CI 11.2 to 14.9). The median overall survival was 17.7 months (95% CI 13.1 to 21.6) and 20.5 months (95% CI 16.9 to 26.9) for patients reaching the sequence 2 (n=65). Conclusion Although the stringent primary endpoint was not met, this stop-and-go strategy with platinum-based chemotherapy plus bevacizumab continuation beyond progression compares favourably with standard schedule, deserving to be further studied in advanced non-squamous NSCLC.

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

This article surveys the growing research programme on the duration of cabinet ministers. It examines some of the conceptual and methodological issues confronting research, including the nature and measurement of durability, ministerial terms and techniques. It considers some of the theories and hypotheses that have been generated by researchers. Using evidence from studies from around the world, it argues that institutional factors, including regime type, constitutional and parliamentary rules, and party systems, affect ministerial durability. Personal ministerial characteristics, such as gender, education and age, also affect durability. It examines future avenues of research in this field.

To evaluate the impact of epidemiological changes observed in 10 years in men with NSCLC on 1-year mortality; to compare prognosis factors of 1-year mortality according to gender.The French College of General Hospital Respiratory Physicians conducted two prospective epidemiological multicentre studies at a 10-year interval (KBP-2000-CPHG and KBP-2010-CPHG). These studies included all adult patients with primary lung cancer histologically or cytologically diagnosed between 1(st) January and 31(st) December for the years 2000 and 2010, managed in the pneumology department of the participating hospitals. A standardised form was completed for each patient. A steering committee checked recruitment exhaustiveness. Vital status 1 year after diagnosis was collected.In 2000 and 2010 respectively, 137 and 104 centres included 3921 and 4597 men and 748 and 1486 women with NSCLC. In 2010 compared to 2000, male patients were older but had better performance status (PS); they were less frequently ever-smokers and heavy smokers; their cancer (usually diagnosed at advanced stage) was more often adenocarcinoma (p0.0001). In 10 years, 1-year mortality has significantly decreased in men (from 61.2% to 56.6%, p0.0001) and in women (from 58.1% to 50.9%, p0.0001), but remained higher in men than in women leading to increased difference between men and women. Decreased 1-year mortality remained statistically significant after adjustment on age, PS, smoking, and histology (men: OR=0.81, 95% CI=0.73-0.90, p0.0001; women: 0.71, 0.57-0.88, p0.002). Active smoking was not a prognosis factor in men (OR=1.04, CI=0.79-1.37, p=0.78); age (75 years) had less impact on mortality in men than in women (men: OR=1.43, CI=1.22-1.67, p ≤ 0.0001; women: OR=2.32, CI=1.71-3.15; p0.0001).The improved 1-year survival in 2010 as compared with 2000 was independent of age, smoking, PS, and histology, suggesting that it reflected new treatment and strategy efficacy. One-year mortality remains higher in men than in women.

EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a “smoker-like” somatic profile compared with unexposed never-smokers.Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled.Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers.There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in >5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.

Access to frequencies is a major concern for all satellite systems. Even if the Ka-band is currently lightly used by Satellite Systems, the Regulatory rules which will govern its access to planned new Satellite Communication Systems have started to be changed during the last World Radiocommunication Conferences. This new regulatory environment, which should be finalised at the next World Radiocommunication Conference, will be a key element in the future of the Ka-Band and of the new Satellite Communication Systems which intend to operate in that Band. The regulatory status of the Ka-Band has dramatically changed at the WRC-97 and new, important changes may happen at the next World Radiocommunication Conference. This paper presents the regulatory status before and after WRC-97. The presentation of the available regulatory tools before WRC-97 (Article S22.2 and Resolution 46) is made in order to demonstrate their inadequacy to allow the emergence of new techniques to improve the efficient use of the spectrum. Detailed description of the relevant new ITU-R resolutions which deal with the sharing between NGSO-FSS and GSO-FSS or other services, explains which opportunities are offered to the new NGSO-FSS systems which intend to operate in this band and which constraints they will have to cope with. A detailed presentation, sub-band by sub-band, of the applicable resolutions and their meaning allows us to clarify the intricate and various regulatory tools governing the use of the Ka-Band. Another order of complexity of the regulatory environment is expressed through the comparison of the international status, as defined in the Radio regulation, with the frequency allocation Plan set up by the Federal Communication Commission for the USA. The paper ends with an overview of the main upcoming issues for the Ka-Band at the next World Radiocommunication Conference.

Mobile communication satellite systems have regularly made the headlines of space industry publications in the 1990s. This paper adopts a new perspective—how the systems evolve over time—to describe the main technical features of the two main types: • -big LEO systems with voice capabilities: Iridium, Globalstar, Odyssey, Inmarsat P21 • -little LEO non-voice systems: Orbcomm, Starsys. This approach reveals the considerable changes, even upheavals, that have affected the design of system components. The apparent stability in the designs is due to outside observers gradually and perhaps unquestioningly perceiving the changes. People's capacity to forget, compounded by the attraction of innovation, may also have a lot to do with it. We present the likely causes of these changes: regulatory environment, market forces, financial arrangements, being at the early design stage, etc. We also analyze the effects of these forces on the systems, and deduce the general trends.

9077Background: Pemetrexed (Pem) + Cisplatine (Cis) + Bevacizumab (Bev) followed with maintenance therapy (Bev and/or Pem) is a therapeutic standard in advanced non-squamous NSCLC. Methods: A singl...

9005Background: Adding bevacizumab to weekly paclitaxel (wPB) has shown synergistic effect and increased activity in various tumor types. The ULTIMATE study evaluated wPB vs. docetaxel (DOC) as 2nd or 3rd-line treatment in patients with advanced non-squamous NSCLC. Methods: Patients with non-squamous NSCLC progressing after 1 or 2 lines of treatment including platinum-based chemotherapy were randomized 2:1 (stratified by PS, previous lines, prior exposure to bevacizumab) to wPB (paclitaxel 90 mg/m² D1, 8, 15 and bevacizumab 10 mg/kg D1, 15, q28d) or DOC (75 mg/m² q21d) until progression. Patients were allowed to cross-over to the other arm following progression. The primary endpoint was progression-free survival (PFS). Results: From 05/2013 to 08/2014, 166 patients were randomized (wPB: 111, DOC: 55). Clinical characteristics were balanced between both arms. 31% had received previous bevacizumab and 69% had received 1 previous line of treatment. Median follow-up was 28.9 months. The adjusted hazard ratio ...

Background The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. Methods We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm3) and fever (temperature > 38.3°C). Results The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm3. Conclusion Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

Understanding the formation of governments has always been central to political science. Traditionally this topic has been considered from a rational choice theory perspective and the empirical testing of these theories; however neither approach alone is able to explain a large proportion of actual coalition formations. This comparative volume brings together a rational choice theory perspective and the empirical testing of these theories to study government formation. It provides in-depth studies of government formations in Europe that cannot be accounted for by existing coalition theory in order to identify potential explanatory factors that have been neglected so far. These ‘coalition puzzles’ are reconstructed by country experts based on secondary sources, newspaper accounts, internal party documents, and interviews in an effort to understand why particular governments were formed. In conclusion, this book assesses whether new factors can be integrated into rational choice theories or whether these analyses point to the need for a different paradigm. This important volume will be of interest to students and scholars of political science, European politics and comparative politics.

This paper is to describe a system for mobile position reporting of mobiles and remote monitoring (short data messaging). It is based on the use of small satellites (mass The main features of the system are the low development and user costs as well as the worldwide and high capacity capabilities (more than 500 000 mobile terminals per geographical zone). Such a system is economically attractive for companies managing large mobile fleets. It is well suited for a ponctual utilization when real time is not needed.

1. Structural and Strategic Factors Affecting the Hiring and Firing of Ministers 2. Hiring and Firing Ministers under Informal Constraints: Germany 3. Cabinet Dynamics and Ministerial Careers in the French Fifth Republic 4. Choosing, Moving and Resigning at Westminster 5. Italy: the Difficult Road towards a more Effective Process of Ministerial Selection 6. Cabinet Dynamics in Democratic Spain 7. Ups and Downs of Ministerial Careers in a Partitocratic Federal State 8. Portugal: The Primacy of 'Independents' 9. In Tranquil Waters: Swedish Cabinet Ministers in the Post-War Era 10. Constructing and Maintaining Irish Governments 11. More Safe than Sound? Cabinet Ministers in Iceland 12. Learning to Rule: Ministerial Careers in Post-Communist Democracies

TPS8110 Background: The incidence of lung cancer is increasing dramatically in women and displays some specific epidemiological, radiological, clinical and pathological characteristics. Two main me...

e19110 Background: In the last few years, new drugs and strategies have emerged in the management of lung cancer (LC). ESCAP-2011-CPHG, promoted by the French College of General Hospital Respirator...

e19078 Background: In recent years, many major advances have been made in non-small-cell lung cancer (NSCLC), and in particular in adenocarcinoma, but not in SCLC. In 2010, the French College of General Hospital Respiratory Physicians (CPHG) performed a prospective multicentre epidemiological study (KBP-2010-CPHG) to describe the baseline characteristics and management of all new cases of primary lung cancer and to evaluate survival. The present abstract reports results in SCLC patients. Methods: 7,051 patients ≥18 years presenting with a new case of primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010 and managed in the respiratory department of one of the 104 general hospitals participating in the study, were included. A standardised form was completed for each patient. A steering committee checked data collection exhaustiveness. SCLC data were analysed separately. Results: There were 968 SCLC patients: mean age, 65.6 years (+/-10.6); 23.2% female; 4.4% non-smokers (11 % in women), 35.8% ex-smokers, 59.8% current smokers; 63.4% with performance status 0 or 1; 59.9% having lost weight within the previous 3 months (19.8% of whom had lost >10 kg). Main tumour characteristics at diagnosis were: 71.2% stage IV, 24.7% stage IIIA or IIIB, 4.1% of stage 70 (59.1%) than

TPS7111 Background: There are no robust data published on the follow-up after surgery for non-small cell lung cancer (NSCLC). Current international guidelines are informed by expert opinion. Most of them recommend regular follow-up with clinic visit and thoracic imaging, either chest X-ray of Chest CT-scan. The IFCT-0302 trial addresses the question whether a surveillance program with chest CT-scan and fiberoptic bronchoscopy can improve survival compared to a follow-up only based on physical examination and chest x-ray. There is no such trial ongoing over the world. Methods: The IFCT-0302 trial is a multicenter open-label controlled randomized phase III trial. The objective of the trial is to compare two follow-up programs after surgery for stage I-IIIa NSCLC. The primary endpoint is overall survival. Patients are randomly assigned to arm 1, minimal follow-up, including physical examination and chest x-ray; or arm 2, a follow-up consisting of physical examination and chest x-ray plus chest CT scan and fiberoptic bronchoscopy (optional for adenocarcinomas). In both arms, follow-up procedures are performed every 6 months during the first two postoperative years, and every year between the third and the fifth years. The main eligibility criteria include: completely resected stage I-IIIA (6th UICC TNM classification) or T4 (in case of nodules in the same lobe as the tumor) N0 M0 NSCLC, surgery within the previous 8 weeks. Patients who have received and/or who will receive pre/post-operative chemotherapy and/or radiotherapy are eligible. Statistical considerations: 1,744 patients is required. Accrual status: 1,568 patients from 119 French centers had been included. The end of accrual can be expected for September 2012. Ancillary study: Blood samples are collected in 1000 patients for genomic high density SNP micro-array analysis. This collection will contribute to the French genome wide association study (gwas) of lung cancer gene susceptibility, and the genetic factors predictive of survival and lung cancer recurrence will be analyzed.

Background: Sorafenib has a well known efficacy in patients with advanced hepatocellular carcinoma (HCC). Sorafenib displays antiangiogenic effects by targeting receptors for VEGF (VEGFR2 and VEGFR3) and PDGF (PDGFRβ) and blocks cancer cell proliferation by targeting RAF/MEK/ERK signalling. However, disease-stabilizing effects are eventually followed by emergence of resistance in patients. The aim of the present work was to describe mechanisms associated with acquired resistance to sorafenib. Materials and Methods: Cell proliferation and clonogenic survival were evaluated in sorafenib-sensitive and -resistant HCC models. Invasiveness of cells was determined by Matrigel invasion assay. qRT-PCR and western blot assays were used to assess a panel of genes and proteins. In vivo sorafenib efficacy was determined in SCID mice bearing SK-HEP1 xenografts. The drug was administered orally, once daily at dose levels of 10 and 30 mg/kg until sorafenib-resistance appearance, starting when tumors were detectable (100-300mm3). Results: The SK-sora cell line was established from the parental SK-HEP1 cell line using a stepwise exposure to increasing sorafenib concentrations for more than 6 months. Exposure to 48-hour sorafenib led to IC50s of 8.3 and 15.9 µM in SK-HEP1 and SK-sora cells, respectively. Clonogenic assay also indicated a significant sorafenib resistance in SK-sora cells. Sorafenib-resistant cells did not display cross-resistance to sunitinib, another multitarget inhibitor. In addition, 30 days sorafenib withdrawal did not restore the sensitive to the drug in Sk-sora cells. Protracted exposure to sorafenib led to a 3-fold increase mRNA expression of VEGFA, VEGFD, erbb4, IGFR1, CXCL12 (SDF-1α) and MIF in SK-sora respect to parental SK-HEP1 cells. In addition we observed a basal up regulation of MAPK and AKT survival signalling pathways as measured by p-ERK1/2, p-AKT and p-S6rp levels in SK-sora cells. Matrigel assay revealed a 3 fold (p Conclusions: Our data show that acquired resistance to sorafenib is associated with the activation of the AKT and MAPKs pathways together with an increased invasion in HCC cells. The role of CXCR4/CXCL12 axis in this model will be explored. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4266. doi:10.1158/1538-7445.AM2011-4266

The effect of inicarone (L7035), a potent fibrinolytic, alone or in combination, was investigated on spontaneously metastasizing Lewis lung carcinoma (implanted intramuscularly) to verify whether it could prevent the formation of metastases. After intraperitoneal and oral administration, inicarone did not show any cytotoxicity since the survival of animals was not prolonged. Its activity was compared to that of warfarin, an anticoagulant: both drugs were inactive when administered in curative treatment and inicarone even enhanced the number of lung metastases. When administered in combination with cyclophosphamide, an antiproliferative agent, inicarone did not induce any synergism or antagonism, but this combination did not inhibit tumour growth or metastasis spreading. Moreover, when inicarone was combined with a potent antimetastatic agent, Nocodazole, it was shown to be in competition with the latter agent and totally overshadowed its activity; since inicarone had no antimetastatic effect, the number of metastases rose dramatically.

Summary As a follow-up to our initial results on the antineoplastic activity of α-1,3,5-triglyciyl-s-triazinetrione (αTGT, NSC-296934, Teroxirone), many new epoxyde derivatives were tested against murine tumours, mostly against P388 leukemia, to determnie their anti-neoplastic role and to characterize their specific effect against tumour cells in vivo , as well as to select an analogue with higher anti-cancer properties and superior pharmacological properties. triglycidyl urazol (TGU, NSC-332488) showed the highest therapeutic activity and a good level of water-solubility which makes this agent a good candidate for phase-one clinical trials.

The antitumor properties of the α and β stereoisomers of 1, 3, 5 -triglycidyl-s-triazinetrione (TGT) were investigated on various transplantable mouse tumor systems. Although the two stereoisomers displayed a high therapeutic activity against P 388 and L 1210 leukemias when administered i.p., α-TGT was superior to the β form in prolonging the lifespan of treated animals and in inducing long-term survival: 70% of long-term survivors over 90 days of treated animals as compared to controls. α-TGT also demonstrated antitumor effect against advanced L 1210 leukemia (ILS: 119% at 50 mg/kg × 9 ) and was still very active when administered orally against i.v. or ascitic L 1210 leukemia while its activity when administered i.p. against i.c. L 1210 was moderate and yet significant. The i.p. treatment with α TGT significantly inhibited the primary tumor growth and lung metastases of Lewis lung carcinoma. Finally, the high in vivo activity of α-TGT on normal P 388 cells and on a subline of this leukemia markedly resistant to cyclophosphamide (Cy) is a further element warranting studies with this agent.

The anti-tumour properties of Cy 233, a new nitrosoureido sugar, were investigated in two murine solid tumours: B16 melanoma and subcutaneously implanted colon adenocarcinoma. Injected i.v., Cy 233 exerted a strong anti-tumour effect against the established B16 melanoma: long-term survivors were recorded with all schedules of treatment. The drug was even more effective against advanced colon 38 adenocarcinoma: it produced a high percentage of total tumour regression, regardless of the route of administration (i.p., i.v., p.o.). The marked in vivo activity of Cy 233 against advanced colon 38 adenocarcinoma, which is known to be resistant to such major anti-cancer drugs as BCNU and chlorozotocin, its water solubility and its stability in aqueous media are further elements warranting toxicological and clinical studies of this agent.

Clinical interest in AMSA, [ 4′-9 (acridinylamino)methanesulfon- m -anisididel has grown recently because it has shown remarkable activity in the treatment of adult myelogenous acute leukaemia. In the present investigation on two experimental murine tumours, namely L 1210 leukaemia and B 16 melanoma, m-AMSA was administered in association with BCNU, melphalan (MLP) and DTIC. The therapeutic activity of the AMSA-MLP-BCNU combination in murine L 1210 leukaemia was compared to that of the MLPBCNU-DTIC combination. These two associations proved to be very active ( 30 % cures were recorded on day 60 ). The dose levels of the drugs used in the combination represent only 30–50 % of the optimal dose of the same drugs given separately. When DTIC was added to the AMSA-MLP-BCNU combination, considerable lengthening of survival time as well as up to 7 cures out of 10 mice on day 60 were recorded. However, none of the combination chemotherapy was able to induce 10 cures (out of 10 mice) like treatment with BCNU, at optimal dose.

The antitumour properties of α/β-triglycidylurazol (TGU) were investigated on various transplantable mouse tumour systems. A high rate of cures of P388 and L1210 leukaemias was obtained with this compound. TGU also had an antitumour effect against B16 melanoma, the colon 38 tumour and the advanced RC renal carcinoma, producing a total regression of the tumour. Finally, the marked in vivo activity of TGU against a subline of P388 leukaemia totally resistant to cyclophosphamide (CP), its good water-solubility (7%) and its stability in neutral pH are further elements warrranting clinical studies with this agent.

The RC tumor, originally a renal adenocarcinoma very sensitive to different classes of chemotherapeutic agents, maintained in CDF 1 mice, was examined for its ability to metastasize. When inoculated into the foot (with 10(7) tumor cells), bulky metastases developed in the popliteal and para-aortic lymph nodes, in a constant and reproducible pattern, producing a massive microscopic invasion of the liver, the lungs and the spleen. The antigenicity tests demonstrated a low immunogenicity of the tumor. Chemotherapy assays showed that adriamycin and vincristine were effective against metastatic dissemination when administered early after tumor cell inoculation and principally when combined with excision of the tumor-bearing leg. The RC model appears to be suitable for the study of lymph node metastasis and could be used in chemotherapy trials of new drugs potentially effective against metastases of the lymphatic system.