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1.
Cancer Med ; 7(7): 3278-3291, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29845746

ABSTRACT

Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1-2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT-TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10-5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFß pathway. EMT-TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.

2.
Case Rep Oncol ; 9(3): 526-529, 2016.
Article in English | MEDLINE | ID: mdl-27790115

ABSTRACT

Gastrointestinal metastases from lung cancer are rare and usually asymptomatic. We report a case of small bowel metastases from primary lung cancer revealed by abdominal pain and severe recurrent anaemia. The diagnosis was obtained with capsule endoscopy. This non-invasive procedure thus represents a valuable method contributing to a rapid and detailed diagnosis while reducing underdiagnosis, and it should thus be considered for lung cancer patients complaining of abdominal symptoms, which may indeed be related to gastrointestinal metastases.

3.
Clin Lung Cancer ; 16(6): 496-506, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26071190

ABSTRACT

UNLABELLED: Extrapolation of clinical trials results to the general population is always challenging. We analysed 1047 patients diagnosed with an advanced stage disease between 1998 and 2005 in a french administrative department and found a good spread of modern chemotherapy since 1998 and targeted therapy since 2002. Moreover, the outcomes in patients treated according to guidelines are very proximal from those obtained in clinical trials. BACKGROUND: Management of metastatic non-small-cell lung cancer has considerably evolved during the past 2 decades. In this study we aimed to assess how treatments have spread at a population-based level and their effect on survival. PATIENTS AND METHODS: Medical records of patients diagnosed from 1998 to 2005 in the French department of Bas-Rhin were checked to collect data on patient characteristics and treatments received. Multivariate analysis of survival was performed using pretherapeutic and therapeutic factors including targeted therapies received as third-line treatment. RESULTS: We included 1047 patients with stage IIIB to IV non-small-cell lung cancer. The proportion of patients who underwent chemotherapy increased from 373/471 (79.2%) to 491/576 (85.2%) over the 1998 to 2001 and 2002 to 2005 periods, and there was an increased use of third-generation drugs associated with platin. Third-line treatment was gefitinib or erlotinib in 73/155 (47.1%) of the cases among patients diagnosed from 2002 to 2005. Compared with older agents, targeted therapy administered as third-line treatment was associated with a longer survival but there was no significant difference in survival with recent chemotherapy agents in multivariate analyses (hazard ratio, 0.773; 95% confidence interval, 0.445-1.343). CONCLUSION: Results of our study showed a good spread of modern chemotherapy and targeted therapy use at a population-based level. However, even if the general outcomes were improved along the years, the results observed in real clinical practice were slightly different from those reported in clinical trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Population Groups , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Female , Follow-Up Studies , France , Gefitinib , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Molecular Targeted Therapy , Neoplasm Staging , Platinum Compounds/administration & dosage , Platinum Compounds/adverse effects , Quinazolines/administration & dosage , Quinazolines/adverse effects , Survival Analysis , Treatment Outcome
5.
Clin Cancer Res ; 20(17): 4613-24, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-25013125

ABSTRACT

PURPOSE: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations. EXPERIMENTAL DESIGN: A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform. RESULTS: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%). CONCLUSION: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer.


Subject(s)
ErbB Receptors/genetics , Lung Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , Receptor, ErbB-2/genetics , ras Proteins/genetics , Adult , Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Class I Phosphatidylinositol 3-Kinases , DNA Mutational Analysis , DNA, Neoplasm/blood , ErbB Receptors/blood , Female , High-Throughput Nucleotide Sequencing , Humans , Lung Neoplasms/blood , Lung Neoplasms/pathology , Middle Aged , Neoplastic Cells, Circulating/pathology , Proto-Oncogene Proteins/blood , Proto-Oncogene Proteins B-raf/blood , Proto-Oncogene Proteins p21(ras) , Receptor, ErbB-2/blood , Smoking , ras Proteins/blood
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