Five-year survival and prognostic factors according to histology in 6101 non-small-cell lung cancer patients.

OBJECTIVE: To estimate five-year survival in non-small-cell lung cancer (NSCLC) patients according to histology and to identify independent prognostic factors by histology. METHODS: Data were obtained during the KBP-2010-CPHG study, which included all new cases of primary lung cancer diagnosed in 2010 in 104 non-academic hospitals. RESULTS: In all, 3199 patients had adenocarcinoma (ADC), 1852 squamous cell carcinoma (SCC), 754 large cell carcinoma (LCC). Five-year survival was 13.3% [12.1%-14.5%] for ADC, 14.3% [12.7%-16.0%] for SCC, 9.6% [7.6%-11.9%] for LCC (P<0.001). Performance status, weight loss prior to diagnosis and tumour stage were consistently significant independent prognostic factors. Age (>70 years; P=0.004), male gender (P<0.001), and smoking (P<0.001) were independent negative prognostic factors for ADC. Epidermal Growth Factor Receptor (EGFR)-mutation tests, performed in 1638 ADC patients, were positive for 186. Five-year survival was 14.7% [10.3%-21%] and 10.9% [9.4%-12.6%] for mutated and wild-type EGFR, respectively (P<0.001). EFGR mutation was an independent positive prognostic factor (HR=0.5 [0.4-0.6], P<0.001); however, the proportional hazards assumption was not fulfilled and hazards were inverted after 35 months. CONCLUSIONS: Five-year survival in patients managed in French non-academic hospitals for primary NSCLC in 2010 remained poor (<15%), whatever the histologic type. The independent negative prognostic factors for five-year survival were: weight, particularly weight loss prior to diagnosis; smoking (active or former) at diagnosis in ADC and LCC and smoking level at diagnosis in smoker patients with SCC. The independent positive prognostic factors were young age and female gender for ADC.

[Second- or third-line treatment with erlotinib in EGFR wild-type non-small cell lung cancer: Real-life data]. / Erlotinib en 2e ou 3e ligne pour les cancers bronchiques non à petites cellules sans mutation de l'EGFR : données en vie réelle.

INTRODUCTION: The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. METHODS: The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. RESULTS: Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). CONCLUSION: Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.

[First treatment strategies in the 2 years following lung cancer diagnosis. ESCAP-2011-CPHG, a real-life study carried out in French general hospitals]. / Stratégies thérapeutiques les 2 premières années après un diagnostic de cancer du poumon. ESCAP-2011-CPHG, étude en situation réelle réalisée dans les hôpitaux généraux français.

INTRODUCTION: The objective of the ESCAP-2011-CPHG cohort study was to perform a real-life analysis of therapeutic strategies used during the first 2years of follow-up after a diagnosis of primary lung cancer. This paper presents the study and its first results in non-small-cell lung cancer (NSCLC). METHODS: Pulmonologists in the respiratory disease departments of 53 general hospitals consecutively included all patients aged 18years and over with lung cancer newly diagnosed in 2010. RESULTS: Of the 3943 patients included, 3418 (mean age: 65.4 years; male: 76%; never smokers: 12%) had NSCLC (adenocarcinoma: 53%; stages 0-II, IIIA, IIIB and IV: 18, 14, 9 and 59%, respectively). Mean follow-up was 13.2 (SD: 10.1) months; mean number of strategies implemented was 2 (SD: 1.3). Overall, 62% of patients had chemotherapy in the first strategy (74% in the second strategy); the rate of chemotherapy alone increased from 6 to 56% with cancer stage. CONCLUSIONS: ESCAP-2011-CPHG opens the way to many possible analyses of the therapeutic strategies currently implemented in French hospitals, comparing strategies, survival or patient characteristics.

[Therapeutic strategies in patients undergoing surgery for non-small cell lung cancer. Results of the ESCAP-2011-CPHG study, promoted by the French College of General Hospital Respiratory Physicians (CPHG)]. / Stratégies thérapeutiques chez les patients opérés pour un carcinome bronchique non à petites cellules. Résultats de l'étude ESCAP-2011-CPHG réalisée par le Collège des pneumologues des hôpitaux généraux (CPHG).

BACKGROUND: The aim of ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, was to describe therapeutic strategies in lung cancer in the first 2 years after diagnosis, in a real-life setting. This article focuses on patients undergoing surgical management of a non-small cell lung cancer (NSCLC). METHODS: A prospective multicentre study was conducted in 53 French general hospitals. For each patient with lung cancer diagnosed in 2010, a standardised form was completed following each change in treatment strategy up to 2 years after diagnosis. RESULTS: Overall, 3418 of the 3943 included patients had NSCLC. 741 patients (21.7%) underwent curative surgery (stage 0-II, IIIA, IIIB, and IV: 65%, 27%, 3% and 5%, respectively). The therapeutic strategy changed less often in surgical than non-surgical patients and average follow-up time was longer: 23.3 months (SD: 9.3) versus 10.4 months (SD: 9.5) for non-surgical patients. Among patients with a surgical first strategy (92.6% of surgical patients as a whole), 56.9% did not receive any other treatment, 34.7% received chemotherapy, 5.9% radio-chemotherapy, 2.6% radiotherapy. At the end of follow-up, 55.8% were still alive without any other strategy, 13.1% had died, and 31.1% had received at least one more strategy. Among patients with a surgical second strategy, 63% had received chemotherapy alone during the first strategy. CONCLUSIONS: ESCAP -2011- CPHG assessed everyday professional practice in the surgical management of NSCLC in general hospitals. It pointed out the discrepancies between current guidelines and the therapeutic strategies applied in real life conditions.

Effect of ionic radii on the Curie temperature in Ba1-x-ySrxCayTiO3 compounds.

A series of Ba1-x-ySrxCayTiO3 compounds were prepared with varying average ionic radii and cation disorder on A-site. All samples showed typical ferroelectric behavior. A simple empirical equation correlated Curie temperature, TC, with the values of ionic radii of A-site cations. This correlation was related to the distortion of TiO6 octahedra observed during neutron diffraction studies. The equation was used for the selection of compounds with predetermined values of TC. The effects of A-site ionic radii on the temperatures of phase transitions in Ba1-x-ySrxCayTiO3 were discussed.

[Comorbidities of COPD]. / Les comorbidités dans la BPCO.

COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patients.

Antepartum fetal heart rate monitoring. A semi-quantitative evaluation of the 'non-stressed' fetal heart rate.

1964 recordings (from 246 patients were analysed on the basis of a semi-quantitative evaluation of base-line heart rate variability. All the tracings were obtained in the antepartum period, between the 20th wk of pregnancy and prior to the onset of labour. None of the recordings were made during labour or after induction of uterine activity so that a 'non-stressed' fetal heart rate test was obtained in every case. The percentage of flat tracing in each recording and the presence of sinusoidal patterns were compared with the neonatal outcome. When the tracings included a more than 50% flat pattern, 81.8% of the babies were distressed at birth. When a less than 50% flat recording was present only 11.4% of the neonates were distressed. Sinusoidal patterns were more frequently associated with abnormal tracings including those with more than 50% flat recordings. The presence of sinusoidal features did not significantly influence the neonatal outcome for tracings with a less than 50% anomaly: conversely sinusoidal patterns superimposed on a more than 50% flat tracing were predictive of fetal compromise and neonatal distress in 100% of the cases. These results allow to advocate the use of 'non-stressed' antepartum fetal heart rate monitoring, as a reliable test in the management of high risk pregnancies.

Antepartum fetal heart rate monitoring. II. Deceleration patterns.

Fetal heart rate was studied during the antepartum period in 246 patients, yielding a total of 1964 recordings. The following parameters were evaluated and correlated: --the semi-quantitative assessment of fetal heart rate instability (as expressed by the percentage of duration of flat traces); --the presence of decelerations and their relationship to the presence or absence of uterine contractions; --the neonatal condition. Overall, 50% of the patients exhibited uterine contractions while 30% contained decelerations patterns either occurring spontaneously or in association with uterine contractions. A definite relationship was observed between the presence of severe decelerations (irrespective of the time relationship with any uterine contraction) and poor neonatal outcome. A relationship does exist between the presence of severe decelerations and flattening in the recording, which, as demonstrated in the previous part of the paper also exhibited a strong positive relationship with the neonatal outcome. When one considers the different degrees of flattening, it appears that a further correlation between decelerations and neonatal state is demonstrable only in the case of a 10--50% flat recording. Here the probability of a distressed baby is 20% in the absence of decelerations, but 43.4% in the presence of decelerations. In other cases (i.e., less than a 10% or more than a 50% flat recording) the pronostic significance of the instability of the record is not significantly modified by he presence or absence of decelerations. These results indicate that consideration of decelerations is only advisable in these cases where instability is moderately affected (flattening in 10-50% of the record) and that the use of the oxytocin challenge test OCT may be reserved for such cases, when these are neither spontaneous contractions nor decelerations and not contraindications present.

Antepartum fetal heart rate monitoring. III. Fetal movements and accelerations in fetal heart rate.

This third part of the paper deals with the study of the relationships between fetal movements, fetal heart rate accelerations associated with such movements, fetal heart rate instability and neonatal outcome. No correlations has been found between absence of fetal movements and neonatal distress. A correlation has been found between the lack of fetal heart rate accelerations, the flatness of the record and poor neonatal outcome. In extreme situations (i.e. flatness in less than 10% of the record or in more than 80%) the presence or absence of accelerations does not add further useful information. Such information, however, is gained in the intermediary situations (the 'combined' recordings) and particularly when the record is between 51 and 80% flat where there appears to be an 85.6% risk to the fetus. Consequently, when trying to analyse an antenatal record it seems advisable to take primarily into account the percentage of flat recordings (providing the records are numerous enough and of sufficient length). Then, in records between 10 and 50% flat, the presence or the lack of spontaneous decelerations requires consideration whereas, when the record is between 51 and 80% flat, it is the presence or absence of fetal heart rate accelerations which is important.

[Severe pneumonia with a pneumococcal aspect during an ornithosis outbreak]. / Pneumopathies sévères d'allure pneumonique, au cours d'une épidémie d'ornithose.

OBJECTIVES: To describe the clinical, radiological and biological features of Chlamydia psittaci pneumonia. METHODS: A pneumonia outbreak occurred in a healthy middle-aged population working in a poultry slaughterhouse. Systematic serology (2 samples at 5 weeks intervals) provided the diagnosis of Chlamydia psittaci pneumonia in 6 patients. Patient files were analyzed retrospectively. RESULTS: The clinical presentations in this series of pneumonia were particularly homogeneous with a pneumococcal profile in all 6 cases: sudden onset, temperature above 39 degrees C, lobar alveolar involvement, hypoxemia, hyperleukocytosis and liver dysfunction. One case of hallucinatory delirium was observed. The patients were given spiramycin (9 million units per day for 3 weeks) and all recovered rapidly with no complications. CONCLUSION: The unusual virulence of the Chlamydia psittaci and very important inoculum were probably involved in this outbreak because of the severity of the pulmonary features and the short exposure of some patients to the bacteria. These cases suggest that the prevention of ornithosis in poultry slaughterhouses should be reinforced.

[Pulmonary malacoplakia caused by Rhodococcus equi in AIDS: a case report]. / Malacoplasie pulmonaire à Rhodococcus equi au cours du SIDA: à propos d'un cas.

We describe the observation of a right upper lobe consolidation with cavitation produced by Rhodococcus equi in a patient suffering from AIDS. The inefficacy of a prolonged antimicrobial therapy adapted against R. equi led to a right upper lobectomy. The histopathology showed a pseudotumoral mass, with dense infiltration of macrophages containing Michaelis-Gutmann bodies, which was positive for the culture of R. equi. Pulmonary malacoplakia with Rhodococcus equi was diagnosed. This pathology should be evoked when a R. equi pneumonia persists despite a right management of treatment for several months. The features of pneumonia with Rhodococcus equi and of pulmonary malacoplakia are taken from a literature review.

[Use of sedation in the palliative care situation by respiratory physicians]. / Représentation de la sédation en situation palliative chez les pneumologues.

INTRODUCTION: The prognosis of advanced stage chronic lung disease, including lung cancer, is often poor and associated with uncomfortable symptoms for the patient, especially in the end of life phase. In the case of intolerable symptoms, refractory to maximal treatment, sedation may then be considered. This is sometimes a source of confusion and difficulty for clinicians who need to know the official guidelines. The purpose of this study was to investigate the use of sedation by respiratory physicians, in order to understand their difficulties in these complex situations. METHOD: The study was conducted using semi-structured, anonymous interviews of volunteers. The topics discussed included their definition of sedation, its indications, their possible difficulties or reluctance in using it, the information given to the patient and the traceability of the sedation prescription. RESULTS: All respiratory physicians agreed to participate in the study, indicating a major interest in this topic. No sedation decision is taken without careful consideration. The majority of physicians understand the difference between anxiolysis and sedation, most defining the latter as using a drug to sedate a patient faced with uncontrollable symptoms. All doctors refused to link sedation to euthanasia, although half expressed a feeling of causality between sedation and the patient's death - knowing that few consider the possibility of transient sedation. The main reluctance among doctors is in chronic respiratory insufficiency. Any decision concerning sedation should be discussed beforehand with the care team and the resident in charge of the patient, but not necessarily with another colleague. There is rarely evidence of this discussion in the medical records or of the information given to the patient and his family, thus increasing the difficulties of decision-making, especially at nights or weekends. The decision to start sedation is seen as difficult because it presupposes that a life-threatening short-term prognosis has been already been given to the patient. CONCLUSIONS: In this medical population, already aware of palliative care issues, the majority of respiratory physicians know the definition, the indications for sedation and the principles of collective decision, but few are aware of the need of regular reappraisal of the sedation, to record it, and of its potential reversibility. There is, therefore, a clear need for regular and further training of clinicians to improve their professional practice.

[Severe pulmonary involvement in the course of type 1 neurofibromatosis]. / Atteinte pulmonaire sévère au cours de la neurofibromatose de type 1.

Type 1 neurofibromatosis (NF1) is a hereditary disease inherited as an autosomal dominant. Respiratory involvement is rare. We report the case of a woman suffering from NF1 with mutation of the corresponding gene and with respiratory involvement combining diffuse parenchymatous lesions, severe precapillary pulmonary hypertension and an enlarging, spiculated pulmonary nodule, very suspicious of malignancy, though histological examination was not possible on account of the patient's poor respiratory function. There was progressive deterioration of the patient's respiratory condition, leading to death, despite the introduction of oral therapy combining a phosphodiesterase 5 inhibitor and an endothelin receptor antagonist. Our case illustrates the development of multiple severe respiratory pathologies in the setting of NF1. The specific contribution of the NF1 gene mutation in the pathophysiology of these different pulmonary manifestations needs to be examined in detail.

[Ten-year evolution in non-small-cell lung cancer according to sex. Results of the KBP-2010-CPHG study by the College of General Hospital Respiratory Physicians]. / Évolution en 10ans du cancer bronchique non à petites cellules en fonction du sexe. Résultats de l'étude KBP-2010-CPHG du Collège des pneumologues des hôpitaux généraux.

INTRODUCTION: Comparison by sex and presenting features between 2000 and 2010 of the characteristics of new cases of non-small-cell lung cancer (NSCLC). METHODS: Observational KBP-2010-CPHG study similar to KBP-2000-CPHG. Both studies were promoted by the French College of General Hospital Respiratory Physicians (CPHG). KBP-2010-CPHG collected data for 6083 NSCLC diagnosed between January 1st and December 31st, 2010, and followed in the respiratory departments of 119 French general hospitals. RESULTS: In 2010, 24.4 % of the patients were women (16 % in 2000, p<0.0001). Compared to men, women were more commonly non-smokers (34.2 vs 4.7 %) or lighter consumers (37.2 vs 43.7 pack per years) (p<0.0001). Their tumours (mostly adenocarcinoma: 64.6 vs 48.7 %, p<0.0001) were more frequently diagnosed at stage IV (62.4 vs 56.9 %, p=0.0008). EGFR mutation research was more frequently performed (48.5 vs 31.0 %, p<0.0001) and positive (20.6 vs 5.2 %, p<0.0001) in women than men. Their treatment more frequently included targeted therapy (13.4 vs 5.7 %, p<0.0001). Compared to 2000, the percentage of non-smokers increased in men (4.7 vs 2.5 %, p<0.0001) while remaining stable in women (36.1 vs 34.2 %, p=0.32). The percentage of adenocarcinomas increased, particularly in men (48.7 vs 31.5 %, p<0.0001). CONCLUSIONS: The percentage of women with NSCLC has increased in 10years in France. In 2010, the main gender differences persist, but have decreased with the increasing proportion of non-smokers and adenocarcinomas in men. Various hypotheses to explain these changes are discussed.

[Drug-induced pneumonitis due to sirolimus: an interaction with atorvastatin?]. / Pneumopathie médicamenteuse sous sirolimus: interaction avec l'atorvastatine?

INTRODUCTION: Sirolimus is an immunosupressant used in renal transplantation because of its lack of nephrotoxicity. We report four cases of pneumonitis due to sirolimus, possibly revealing an interaction with atorvastatin. CASE REPORT: Four patients (previously on long-term treatment with atorvastatin) presented with respiratory symptoms between 3 and 56 months after starting treatment with sirolimus following renal transplantation. Thoracic CT scans showed bilateral areas of peripheral alveolar consolidation. Bronchial lavage showed a lymphocytic alveolitis. Open-lung biopsy showed organizing pneumonia associated with diffuse alveolar damage and caseating granulomata. We attributed the pneumonitis to sirolimus on account of clinical and radiological resolution within 1 to 6 months of stopping treatment. We raise the possibility of an association between sirolimus and atorvastatin by competition for their hepatic degradation pathway via cytochrome P450 3A4. CONCLUSION: Sirolimus causes drug-induced pneumonitis that is predominantly an organizing pneumonia. Atorvastatin may encourage its development by competition with sirolimus in the liver.