Lung Cancer in Patients with Severe Idiopathic Pulmonary Fibrosis: Critical Aspects

Abstract

Abstract. Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease limited to the lung with an undefined etiopathogenesis and a very short life expectancy (less than 5 years). IPF susceptibility has been associated with several genetic and environmental risk factors and the prognosis isIdiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with poor prognosis and an undefined etiopathogenesis. Several genetic and environmental risk factors for IPF have been identified including cigarette smoking, metal dust and other pollutant exposure, genetic mutations and polymorphisms (1-5). IPF prognosis is really poor (less than 5 years) and is conditioned by comorbidities negatively affecting patients' quality of life and survival (e.g. gastro-esophageal reflux, depression, venous thromboembolism, pulmonary hypertension and other cardiovascular disorders, and lung cancer) (6-10). The incidence of pulmonary neoplasm is much higher in IPF patients than in the general population (11). Ozawa et al. (12) for instance, reported 3.3%, 15.4% and 54.7% of lung cancer incidence in IPF patients after one, five and ten years of follow-up, respectively (12). Common mechanisms shared by the two diseases remain unknown. An aberrant expression of miRNAs regulating non-small cell lung cancer (NSCLC) and IPF has been suggested together with a crucial role of tyrosine kinase inhibitor directed against growth factors (plateletderived growth factor, vascular endothelial growth factor and fibroblast growth factor) (13,14).Lung cancer (LC) significantly reduces survival of IPF patients, including patients with combined pulmonary emphysema and pulmonary fibrosis (15). It generally occurs in the peripheral areas of the lower lobes, where fibrotic changes are predominant. In particular, LC develops from honeycomb areas or in the border between honeycombing and non fibrotic areas and the squamous cell carcinoma is the predominant histological type (16,17). Invasive diagnostic or therapeutic procedures for neoplasms promote the development of Acute exacerbations (AE) in 80% of IPF patients and the lung surgical treatment puts about 1/5 of them at high risk of death (17,18). A perioperative Pirfenidone treatment has recently been proposed to reduce the incidence of postoperative acute events (18)(19)(20). In this context, the therapeutic management of LC is a difficult task and is still questioned, especially in IPF patients with severe fibrotic involvement, whether the tumor should be treated or not (21,22). Although Lee et al. (15) reported that radiotherapy and surgical treatments of LC result in a reduced survival of IPF patients, according to Kumar et al. (19) lung resection in selected cases can improve their survival. Furthermore, Tomassetti and colleagues (21) have suggested that in mild IPF patients the sublobar resection in 773

Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets

“…Similarly to fibrotic lesions, lung carcinomas are generally more frequently found in the peripheral area of the lungs in IPF patients, i.e., in the lower lobes [3,8,16,25,30,31,32], and are associated with honeycomb lesions, developing from honeycomb areas or in the border between honeycombing and non-fibrotic areas, and epithelial metaplasia [33,34,35]. In general, squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, have been observed more frequently in LC-IPF patients than in IPF patients without lung carcinoma.…”

Stereotactic body radiation therapy (SBRT) in the management of non-small-cell lung cancer: Clinical impact and patient perspectives

“…Idiopathic pulmonary fibrosis (IPF) is among the most severe form of ILD, with a life expectancy of less than 5 years. 58 The incidence of lung cancer in IPF patients is very high, at up to 15% at 5 and 50% by 10 years. 59 While the exact reason for increased cancer pathogenesis in IPF patients is unknown, it has been acknowledged that IPF and lung cancers share up-regulation of common proteins and cytokines.…”

Exhaled Breath Condensate: A Non-Invasive Source for Tracking of Genetic and Epigenetic Alterations in Lung Diseases

“…4,5 Patients with some lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and tuberculosis (TB) are at increased risk for the development of lung cancer. [6][7][8][9] The survival rate tends to be low because most lung carcinomas are diagnosed at an advanced tumor stage so, early diagnosis is the main goal to improve survival rate in lung cancer. 10 Both radiological imaging (CT, PET) and histological examination (bronchoscopy, thoracic needle aspiration or thoracentesis) are expensive and invasive procedures for population screening for lung diseases.…”