Efficacy of First-Line Chemotherapy in Patients with Advanced Lung Sarcomatoid Carcinoma

Background:Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non–small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC.Methods:Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected.Results:Ninety-seven patients were included. Median age was 62 (54–72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non–platinum-based CT (p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8–2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7–7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9–9.0] versus 5.3 months [CI 95%: 2.8–7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio = 0.38 [CI 95%: 0.21–0.59]) and at platinum-based CT (hazard ratio = 0.92 [CI 95%: 0.85–0.99]) was associated with better OS.Conclusion:SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC

No evidence for a pathogen associated with pulmonary MALT lymphoma: a metagenomics investigation

International audienceMucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with chronic antigen stimulation:auto-antigens or of microbial origin. Only one study suggested association betweenAchromobacter xylosoxidansand pulmonary MALT lymphoma. We aimed to investigate the presence of virus or any infectious agents inpulmonary MALT lymphoma by using metagenomic next-generation sequencing (mNGS).All lung samples were centrally reviewed. The t(11;18) (q21;q21) was evaluated by FISH analysis. The snap frozenlarge lung biopsies were analyzed by mNGS. After lung biopsies homogenization total nucleic acids (RNA and DNA)were extracted, amplified and classified according to their taxonomic assignment, after exclusion of host DNA.We included 13 samples from pulmonary MALT lymphoma (mean age: 60.3 years, 7 women, 3 with auto-immunebackground) and 10 controls. The diagnosis of MALT lymphoma was confirmed for the 13 samples, 3 showed API2-MALT1 translocation (23%). No evidence of the presence of a specific pathogen was clearly identified in the groupof patients with pulmonary MALT lymphoma. We identifiedA. xylosoxidanssequence in 4/13 patients and in 4/10controls.This study did not find evidence for a DNA or RNA virus, a fungi, a parasite or a bacteria associated with pulmonaryMALT lymphoma either in the stroma or in tumor cells

Regulator of telomere length 1 ( RTEL1 ) mutations are associated with heterogeneous pulmonary and extra-pulmonary phenotypes

International audienceRegulator of telomere length 1 (RTEL1) mutations have been evidenced in 5-9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1 years (range 28.0-80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2 months and 45.3 months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts

The N-Terminal Domain of cGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus

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Measurement of semi-inclusive pi+ electroproduction off the proton

Semi-inclusive pi(+) electroproduction on protons has been measured with the CLAS detector at Jefferson Lab. The measurement was performed on a liquid-hydrogen target using a 5.75 GeV electron beam. The complete five-fold differential cross sections were measured over a wide kinematic range including the complete range of azimuthal angles between hadronic and leptonic planes, phi, enabling us to separate the phi-dependent terms. Our measurements of the phi-independent term of the cross section at low Bjorken x were found to be in fairly good agreement with pQCD calculations. Indeed, the conventional current fragmentation calculation can account for almost all of the observed cross section, even at small pi(+) momentum. The measured center-of-momentum spectra are in qualitative agreement with high-energy data, which suggests a surprising numerical similarity between the spectator diquark fragmentation in the present reaction and the antiquark fragmentation measured in e(+)e(-) collisions. We have observed that the two phi-dependent terms of the cross section are small. Within our precision the cos2 phi term is compatible with zero, except for the low-z region, and the measured cos phi term is much smaller in magnitude than the sum of the Cahn and Berger effects