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.

Patients with non-small-cell lung cancer harbouring a BRAF mutation: a multicentre study exploring clinical characteristics, management, and outcomes in a real-life setting: EXPLORE GFPC 02-14.

Background: Mutations in BRAF are rare oncogene mutations, found in 2% of non-small-cell lung cancers (nsclcs). Little information is available about the management of patients with BRAF-mutated nsclc, except for those included in clinical trials. We undertook the present study to assess the clinical characteristics, management, and outcomes of those patients in a real-life setting. Methods: This retrospective multicentre observational study included all patients with BRAF-mutated nsclc diagnosed between January 2012 and December 2014. Results: Patients (n = 59) from 24 centres were included: 57.6% men; mean age: 64.5 ± 14.5 years; 82% with a performance status of 0-1 at diagnosis; smoking status: 40.3% current, 32.6% former; 93% with adenocarcinoma histology; 75% stage iv; 78% with V600E mutations; 2 with EGFR and 2 with ALK co-mutations. Of the stage iv patients, 79% received first-line therapy (14.2% anti-BRAF), and 48% received second-line treatment (23.8% anti-BRAF). Response rate and progression-free survival were, respectively, 51.7% and 8.7 months [95% confidence interval (ci): 6.4 months to 15.2 months] for first-line therapy and 35.3% and 4.1 months (95% ci: 2 months to 10.9 months) for second-line treatments. The 2-year overall survival was 58.5% (95% ci: 45.8% to 74.8%). Outcomes in patients with stage iv nsclc harbouring BRAF V600E mutations (n = 32) did not differ significantly from those of patients with other BRAF mutations. Conclusions: In this real-world analysis, most nsclc patients with a BRAF mutation were men and current or former smokers. Survival appears to be better in these BRAF-mutated patients than in nsclc patients without an oncogenic driver.

[Cardiac compression of hydatid origin]. / Compression cardiaque d'origine hydatique.

INTRODUCTION: Cardiac hydatid disease is uncommon and occurs in 0.5 to 2% of patients with hydatidosis. Isolated intrapericardial hydatid cystic disease is extremely rare. OBSERVATION: We report the case of a young woman with cardiac compression due to multiple primary intrapericardial hydatid cysts. Since 1 year, she had gradual general health deterioration including dyspnoea, sweats and weight loss of 8kg. A widening of the mediastinum was observed on chest X-ray. The CT-scan, echocardiography and the dynamic IRM showed multiple mediastinal cysts with mass effect on the heart and main pulmonary artery. The size of the main pulmonary artery was reduced to 5 mm in diameter and the right upper pulmonary vein was nearly closed by posterior cysts. The right and left ventricular ejection fractions were estimated at about 34%. A complete resection of the cysts was performed by sternotomy. The surgical procedure was technically difficult because of major local inflammatory process. The postoperative outcome after an initial pulmonary embolism event was finally favourable. CONCLUSION: Hydatidosis can lead to severe cardiac involvement. These rare forms of hydatid cystic disease must be known even in non endemic regions by surgeons because of increasing mobility of the world's population.

Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study.

UNLABELLED: Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67 ± 12.7 years, women: 69 %, non smokers: 68 %, PS 0-1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients. CLINICAL TRIAL INFORMATION: NCT02293733.

Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study.

BACKGROUND: Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. OBJECTIVE: To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. METHODS: In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. RESULTS: 147 patients were randomized (median age: 60±8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. CONCLUSION: Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status.

Occupational and nonoccupational factors associated with high grade bronchial pre-invasive lesions.

Besides tobacco exposure, factors associated with the development of pre-invasive bronchial lesions are not known. Autofluorescence bronchoscopy was used to assess the prevalence of severe dysplasia and carcinoma in situ (SD/CIS) of the proximal bronchial tree in relation to occupational or nonoccupational carcinogen exposure. Among the 241 individuals in this study, the overall prevalence of at least one SD/CIS was 9% (21 subjects). Multivariable analysis revealed significant and independent associations between presence of SD/CIS and: 1) active smoking, relative to former smokers; 2) presence of synchronous invasive lung cancer; 3) duration of asbestos exposure and; 4) exposure to other occupational carcinogens. The independent associations of synchronous lung cancer with severe dysplasia and carcinoma, after adjusting for both occupational and nonoccupational carcinogen exposures, suggest other mechanisms than a field cancerisation may be involved in the carcinogenesis of these pre-invasive lesions. Moreover, active smokers, patients with recently resected invasive lung cancer and workers occupationally exposed to bronchial carcinogens may represent a population of choice for early cancer endoscopic detection programmes in view of their high severe dysplasia and carcinoma prevalence.

[Unrecognized causes of chronic cough]. / Causes méconnues de toux chronique.

Chronic cough is defined as persistence of the symptom for longer than one month. It is a common reason for consultation. A systematic diagnostic approach based on the history, clinical examination and a number of investigations (chest x-ray, lung function tests, oesophageal pH monitoring and sinus x-rays) reveals the cause in most cases. The main aetiologies are post-nasal drip, gastro-oesophageal reflex, asthma, chronic bronchitis, and the use of angiotensin converting enzyme inhibitors. Nevertheless, in some cases, the cause is not found. In this situation it is necessary to search for less common pathologies where cough is just a symptom of systemic disease, such as connective tissue disorder (Sjogren's syndrome, atrophic polychondritis), vasculitis (Wegener's granulomatosis), Horton's syndrome (cluster headaches), amyloidosis and inflammatory bowel disease. It may also be a matter of local pathology of the tracheo-bronchial tree, such as tracheo-bronchomegaly, tracheopathia osteoplastica, rare or unrecognized infections (whooping cough, post-viral cough, bronchial tuberculosis), reactive bronchial dysfunction, eosinophilic bronchitis or radiologically occult bronchial carcinoma. Il is also necessary to consider vocal cord dysfunction and cough due to medication before accepting a diagnosis of psychogenic cough.

[Pregnancy, tuberculosis and inappropriate antidiuretic hormone secretion]. / Grossesse, tuberculose et sécrétion inappropriée d'hormone antidiurétique.

We report a pregnant woman presenting with seizure secondary to hyponatremia by inappropriate antidiuretic hormone secretion. Aetiology was unknown urinary and lung tuberculosis. This case report presents diagnosis strategy of inappropriate antidiuretic hormone secretion and the arguments for its aetiology.

Follow-up of bronchial precancerous lesions and carcinoma in situ using fluorescence endoscopy.

Little is known about the natural history of precancerous bronchial lesions. Histological changes occurring in 416 bronchial intraepithelial lesions (104 high-risk subjects) were assessed over a 2-yr period, using repeated follow-up autofluorescence endoscopies. During the study, 6 of 36 normal epitheliums became dysplastic; 47 of 152 metaplasia evolved to low-grade dysplasia, two progressed to carcinoma in situ, and one to invasive cancer; 6 of 169 low-grade epithelial lesions progressed to a persistent severe dysplasia; 10 of 27 severe dysplastic lesions and 28 of 32 carcinoma in situ persisted or progressed, respectively (p = 0.0005, severe dysplasia versus carcinoma in situ 24 mo outcome). Carcinoma in situ appeared more frequent in patients with a prior history or concomitant cancer (p = 0.003). Persistence of smoking during the study did not influence high-grade lesion outcome. Progression of low-grade epithelial lesions during the study occurred only in patients with at least a high-grade lesion in another site at baseline (9 of 147 lesions, 6.1%). Our study suggests that low-grade epithelial lesions could be safely followed-up at 2 yr in patients without high-grade lesions at baseline, whereas severe dysplasia should be treated if they persist at 3 mo. Immediate treatment of carcinoma in situ appears warranted.

[Mediastinal leiomyosarcoma]. / Léiomyosarcome médiastinal.

Leiomyosarcomas are extremely rare tumors which develop from smooth muscle, usually in the esophagus and large vessels (inferior vena cava, pulmonary artery, and superior vena cava). In very rare cases, leiomyosarcomas develop from small vessels in the soft tissue of the mediastinum. Clinical expression of mediastinal leiomyosarcomas (dysphagia, dysphonia) is related to their large size and the subsequent compression of mediastinal structures. At pathology examination, the gross aspect is one of a single cell tumor. Microscopically, the tumor may be highly undifferentiated making it necessary to use specific immune markers (actin and desmin) or ultra-structural analysis to establish the diagnosis. Treatment of localized tumors is based on surgical excision, either alone or in combination with radiotherapy of the mediastinum. Chemotherapy, generally dexorubicin, is indicated in case of metastatic dissemination, but outcome remains uncertain. As for all soft tissue sarcomas, the prognosis of mediastinal leiomyosarcoma depends on the size of the tumor, its histological structure and its resectability.

[Limbic encephalitis and SIADH revealing small-cell anaplastic lung cancer: MRI and immunologic findings]. / Encéphalite limbique et SIADH révélant un cancer pulmonaire anaplasique à petites cellules. Aspects IRM et immunologiques.

Paraneoplastic limbic encephalitis (PLE) is a manifestation of clinico pathological entity encephalo-myelo-neuropathy associated with anti-neuronal antibodies type 1 (ANNA-1 also called anti-Hu). Isolated PLE is rare. We reported a case of PLE in a 61-year-old heavy smoker man. An inappropriate antidiuretic hormone secretion syndrome was associated. Cranial MRI showed hyperintensity in amygdalo-hippocampic regions on T2 weighted sequences which appeared hypointense on T1-weighted sequences without gadolinium enhancement. Anti-Hu antibodies were absent in serum and in CSF. Despite chemotherapy, he died 18 months after disease onset. Our patient presented PLE without myelonouropathy and without ANNA-1 which suggests a different immunopathology.