ABSTRACT
Lung cancer is the leading cause of cancer deaths in France, with about 30,000 deaths per year. The overwhelming majority (90 %) are tobacco-related. The prognosis is dark but great therapeutic advances have been made with the development of targeted therapies first and then immunotherapy afterwards. These medications are conditioned to the expression of biomarkers that require specific tools in routine to measure them. We will detail in this chapter several techniques of anatomopathology, cytogenetics and molecular biology necessary for the detection of biomarkers in lung cancers, and their applications in thoracic oncology in 2018.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/diagnosis , Cytogenetic Analysis/methods , High-Throughput Nucleotide Sequencing/methods , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Chromatin Immunoprecipitation/methods , Cytogenetic Analysis/trends , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Sequence Analysis, DNA/methods , Translocation, GeneticABSTRACT
BACKGROUND: Programmed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC). METHODS: This phase II study is designed to administrate three durvalumab IV infusions (10mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (>4cm) or stage II, ≥18 years of age, WHO performans status 0-1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection<85% (P0) is considered unacceptable. P1 hypothesis is of 95%, and with a study power of 90% and an alpha risk of 5% (two-steps Fleming's procedure), 81 patients are required. EXPECTED RESULTS: To establish whether neoadjuvant immunotherapy is feasible and could improve the survival of patients with early-stage NSCLC.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , Feasibility Studies , France , Humans , Immunotherapy/methods , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pneumonectomy , Preoperative Period , Research Design , Young AdultABSTRACT
About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]>3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP<35mmHg without severe right ventricular dysfunction and PVR<4 WU).
