Lung cancer in never smokers (LCINS) is often considered a different disease entity with a distinct molecular sub-classification. Notably, actionable mutations in epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten Rat sarcoma viral oncogene homolog (KRAS) and anaplastic lymphoma kinase (ALK)-rearrangement are three major recurrent oncogenic alterations in LCINS. HER2 and BRAF mutations, ROS1 and RET rearrangements are also included, although these are known to occur with low frequencies. Although the overall response rate (ORR) to EGFR tyrosine kinase inhibitors (TKIs) in unselected patients was only 10 %, subgroup analyses revealed comparatively higher response rates and survival in women, never smokers and Asians harbouring EGFR mutations, suggesting a predictive and/or prognostic significance among patients with mutated EGFR by smoking status. Differences in the prevalence of KRAS mutations between subgroups have also been described: 8 % of never smokers versus 57 % of former/current smokers with lung adenocarcinoma harbour KRAS mutations, and although 3 % to 5 % of unselected patients with lung adenocarcinoma have ALK rearrangements, the frequency appears to be more pronounced in never smokers. There is a suggestion that prognostic and predictive relevance of KRAS mutations varies by smoking status, but it is still less characterized as well as the smoking-related prognostic and predictive value of ALK rearrangement and the other alterations, which are still largely unknown. Clinical trials of lung cancer patients should always be stratified by smoking history and the identification of differences according to smoking status may help optimize future targeted therapies.
The recognition that chronic graft dysfunction after lung transplantation is a heterogeneous phenomenon has led to the introduction of a new term: chronic lung allograft dysfunction (CLAD). An International Society for Heart and Lung Transplantation working group will determine a definition of CLAD in 2014. It is thought that CLAD should not totally replace bronchiolitis obliterans syndrome (BOS), the conventional phenotype of chronic graft dysfunction, but that it should be a more comprehensive category that includes BOS as a purely obstructive disorder. Another phenotype to be included is restrictive allograft syndrome, a restrictive form of graft dysfunction that is distinct from BOS. Neutrophilic reversible allograft dysfunction may be included in CLAD as well. Further discussion is required before including other conditions associated with impaired pulmonary function after transplantation. Recent progress in the management of patients with CLAD includes the development of a series of diagnostic tests and recognition of the benefits of a trial of low-dose azithromycin. Further refinement of our understanding of the pathophysiology of CLAD and clinical care pathways is necessary.
In the majority of pleural effusions, chest radiograph and transthoracic ultrasonography (TUS) are sufficient for clinical management. TUS is able to identify very small volumes of fluid, suggest a malignant etiology, and guide pleural procedures. Computed tomography is of particular value in pleural effusions of uncertain etiology, whereas positron emission tomography and, specifically, magnetic resonance imaging are solely indicated for very select cases. This pictorial review addresses the main radiological signs of frequently encountered causes of pleural effusions.
Fibrotic hypersensitivity pneumonitis (FHP) is a specific form of HP defined by chest imaging evidence or pathologic evidence of fibrosis or scarring. Fibrotic HP appears to be irreversible, is often progressive and frequently indistinguishable from other forms of chronic fibrosing interstitial lung diseases (ILD), in particular idiopathic pulmonary fibrosis (IPF). Accurate diagnosis is a challenge given the diverse and often nonspecific clinicoradiologic patterns, heterogenous clinical course, and a frequent lack of a readily recognizable temporal relationship between exposure to an inciting antigen (IA) and symptoms in more than half of the patients. This chapter focuses on the clinical features, diagnostic evaluation and management of FHP.
Lung cancer has long been regarded as a poor candidate for immunotherapy, because it has a relatively low content of tumor-infiltrating lymphocytes compared with, for example, melanoma. However, new developments in immunotherapy are about to change this situation. Therapeutic vaccines are different from the well-known prophylactic vaccines, in that they are designed to treat patients already suffering from a disease instead of preventing the disease in healthy individuals. Several therapeutic vaccines are in late-stage clinical development for non-small-cell lung cancer (NSCLC). These vaccines use different approaches, including peptides, cell lines or viral vectors, and are used in different settings within the pathology. Some are given as monotherapy, whereas others are combined with traditional therapy for this indication. More recently developed, and very promising, are the checkpoint-blocking antibodies. It is likely that in the future several approaches, including immunotherapy products, will be combined in the evolving standard of care for lung cancer. This review gives a summary of the candidate immunotherapy products currently in late-stage clinical development for NSCLC.
