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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., (Copyright © 2018. Published by Elsevier Masson SAS.)

Erlotinib can be prescribed in the treatment of locally advanced or metastatic non-small lung cancer cell (NSCLC) after failure of at least one prior chemotherapy regimen on the basis of the BR-21 study. Several publications have recently questioned these results. The metabolic imaging of solid tumours by positron emission tomography is a research field that could help customize the treatment of NSCLC and so complement the treatment approaches allowed by genetic analyses. This strategy is part of an innovative "early metabolic look" approach. The primary objective of this study is to determine if metabolic progression observed between the 7th and 14th day after initiation of treatment with erlotinib by 3'-Deoxy-3'-[18F]-Fluorothymidine PET in patients with EGFR naive NSCLC is predictive for morphological progression after 6 to 8 weeks of treatment. A health economic analysis will be conducted. This study is particularly innovative because it begins the exploration of the era of metabolic evaluation of therapeutic response in NSCLC., (Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: In a first study, we identified signatures of 3 mRNAs (semaphorin 3D [SEMA3D], cytokeratin 16 [KRT16] and UL16 binding protein 2 [ULBP2]) associated to response to a cisplatin-vinorelbin chemotherapy and to survival of advanced non-small cell lung cancers (NSCLC)., Material and Methods: The aim of this study was to develop immunohistochemistry tests for KRT16, ULBP2 and SEMA3D and to test proteins expression for prediction of response and survival in biopsies of the same patients., Results: We were not able to reproduce by the protein expression study the signature predicting response to chemotherapy in advanced NSCLC., Conclusion: We highlight the difficulties of translational research in thoracic oncology emphasizing the complexity in obtaining adequate tissue samples and the difficulties in conduction and transposing in routine practice high throughput technique for transcriptomic analyses., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Stereotactic radiotherapy is a standard treatment option for patients with stage I non-small cell lung cancer who are unfit for surgery or who are medically operable but refuse surgery. Comparable overall survival rates in operable patients are also supported by non-randomized single-institution and population based studies. Stereotactic radiotherapy has emerged as an alternative, effective and well tolerated in treating pulmonary oligometastases. The early detection of recurrence is important in the medically operable population for whom curative surgical salvage treatments are still available. A standardized definition of recurrence criteria becomes especially important in that context. In 2012, Huang et al. proposed a follow-up algorithm for these patients, whose different points are discussed in this publication., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Introduction: The inadequate secretion of β-human chorionic gonadotropin (β-HCG) during non-small cell lung cancer (NSCLC) is rare and quite ignored. The dosage of β-HCG is probably not systematically realized in women who are in age of pregnancy and who need chemotherapy (CT) despite the descriptions of cases of prescription of CT against lung cancer in women who were pregnant. The incidence of NSCLC cancer is increasing and the risk to prescribe a CT in a woman who is pregnant is also increasing., Cases Reports: We describe the cases of two women and one man who had an augmentation of the β-HCG plasmatic level before the prescription of CT against lung cancer. In women, the differential diagnostic between inadequate secretion of β-HCG and pregnancy has been a problem., Conclusion: The inadequate secretion of β-HCG during NSCLC is probably not so rare. The dosage of this hormone before each infusion of CT should be systematic to avoid the realization of CT during pregnancy. This raises the question of the method for differential diagnostic between pregnancy and inadequate secretion of β-HCG in young women who suffer from NSCLC, especially when a small level of β-HCG is measured., (Copyright © 2013. Published by Elsevier Masson SAS.)

The Ras/Raf/Mek/Erk pathway is a key component of tumor progression and modulates proliferation, survival, differentiation and angiogenesis. Hyperactivation of this pathway is highly implicated in tumorigenesis especially by gain of function mutation of Kras or Braf. Mek position at the end of the pathway seems to be a promising new therapeutic target in the Kras or Braf mutated cancers. In this review, we aimed at describing the Ras/Raf/Mek/Erk pathway, the new therapeutic approaches in solid tumors and their toxicities. However, there seems to be predictives factors of tumor responses to these new agents and mechanisms of resistance that we will tend to analyse.

Introduction: Few data are available about the predictive value of FDG-PET-CT in the evaluation of the response to chemotherapy of patients with advanced NSCLC and its impact on subsequent survival., Methods: A retrospective study of patients with advanced NSCLC who underwent a FDG-PET-CT before treatment and after three cycles of first-line chemotherapy. Morphological and metabolic responses were assessed respectively using RECIST/OMS and EORTC criteria. The relation between response and survival was analysed through Cox regression models., Results: Fifty-nine patients were included in the study (stage IIIA/IIIB/IV: 9/11/39). Median survival was 40 weeks (44 deaths observed). The evaluation of treatment response (morphological or metabolic, taken alone or combined) in terms of survival failed to identify any difference between responders and patients with stable disease. Only patients with progressive disease had a significantly shorter survival. The negative predictive value of the metabolic response for the morphological response is 0.90 and that of metabolic progression for morphological progression is 0.98., Conclusion: Only progressive disease differs significantly from other types of response with a more sensitive and earlier detection by PET-CT., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

EGFR receptor is expressed on most of the non small cell lung carcinoma (NSCLC) cells. Its relative importance in oncogenesis and tumour progression seems to greatly vary among NSCLC. Two molecules targeting differently EGFR are currently used for the treatment of metastatic NSCLC. cetuximab, a monoclonal antibody directed against the extracellular domain of the receptor, leads to a moderate survival benefit when associated with standard first-line chemotherapy. Erlotinib, a small EGFR tyrosine-kinase inhibitor molecule is used in 2nd or 3rd treatment line. Predictive factors for efficiency of these new treatments are subjects of intense research, in order to allow a better selection of the patients who could benefit from such a strategy.

An impressive number of publications refer to prognostic and predictive factors in lung cancer. TNM classification and performance status significantly influence the choice of treatment and strongly predict patients' survival. Depending on the population studied (small cell or non-small cell cancer, operable or not) other independent factors improve the prediction of prognosis; they are clinical, biological, radiological or molecular and pertain to the tumor or the patient. Molecular targeted therapies development has renewed the interest towards predictive factors. New strategies are developed to explore individual response to treatment such as EGFR tyrosine-kinase inhibitors, without success for anti-angiogenic treatments. Conventional cytotoxic agents may also be customized with predictive factors (i.e. ERCC1 or RRM1). Large multicenter studies are needed to validate new independent prognostic factors and increase our current knowledge aiming at separating patients who will really benefit from therapies of those who will only experience the side effects.

AKT-mTOR pathway is considered as a key actor of the regulation of cell metabolism, interacting in network with multiple pathways implied in immune regulation and carcinogenesis. mTOR inhibitors were initially proposed as immunomodalting agents and are now developed as targeted therapy for non-hematologic solid tumours or lymphomas. This review proposes to synthesize knowledge on the AKT-mTOR pathway and the currently available data for head and neck or pulmonary tumours in order to present the value of these agents in this setting. Rational and preclinic results will then allow us to discuss potential future development of mTOR inhibitors.

Despite the development of new chemotherapy regimens, including platinum-containing combinations, the prognosis of NSCLC remains very poor. Advances in the understanding of cancer biology and more specifically, of cell signalling pathways have led to the identification of several potential molecular targets and to the development of new agents directed against these targets. The most advanced molecular therapies target the EGF (epidermal growth factor) receptor and the angiogenesis pathway. Despite this progress, treatment efficacy (molecularly-targeted therapy or chemotherapy) appears to be very heterogeneous across patients. The current challenge is to be able to define the most relevant patient-tailored treatment, based on clinical, histological or biological markers, in order to improve the benefit and tolerance of antitumor treatments. Discovering new prognostic or predictive biomarkers for lung cancer is one of the main objectives of translational cancer research.

EGFR tyrosine kinase inhibitors are currently included in the therapeutic armamentarium against advanced NSCLC. However, many questions on the use of anti-EGFR treatment in NSCLC still remain to be answered. Although several biological factors that may help identify those who are likely to respond to EGFR-targeted therapies have been reported, their clinical utility in routine practice remains to be determined. Moreover, the better way to combine EGFR targeted therapies with chemotherapy, new biological agents or loco-regional therapies at earlier stages of the disease is still under investigation. Clearly, the results of ongoing and future trials are required for an appropriate use of this new class of agents in NSCLC patients.

Geriatric oncology has become recognised as a discrete speciality. Although there is a strong evidence base for using chemotherapy in patients with advanced non-small cell lung cancer, cisplatin administration is associated with significant toxicity and the evaluation of the risk benefit ratio should be particularly rigorous in elderly patients. With aging, hepatic metabolism, renal excretion, volume of distribution and albumin concentration decrease and drug concentration increases. To plan treatment for elderly patients, a multidimensional geriatric evaluation including not only performance status and the identification of comorbidities, but also an assessment of creatinine clearance, functional (activities of daily living), mental (mini-mental state evaluation and geriatric depression index) and nutritional status should be undertaken. On the basis of this comprehensive geriatric assessment it should be possible to identify three groups of older cancer patients; fit, vulnerable and frail and thus to propose appropriate treatment. Accepting that the ideal form of geriatric assessment remains to be defined, a comprehensive assessment to allow individualised treatment in elderly patients is mandatory.

This article describes a case of lung cancer with associated hypercalcitoninemia in a man with a goitre. The case raises the problem of the differential diagnosis between medullary thyroid carcinoma and a neuroendocrine neoplasm with ectopic calcitonin secretion. The article first reviews the physiology of calcitonin, then outlines the diagnostic tests that are required to investigate hypercalcitoninemia and finally discusses the interpretation of test results.