Idiopathic Pulmonary Fibrosis and Lung Cancer: A Systematic Review and Meta-Analysis.

RATIONALE The association between idiopathic pulmonary fibrosis (IPF) and lung cancer has been previously reported. However, there is the potential for significant confounding by age and smoking, and an accurate summary risk estimate has not been previously ascertained. OBJECTIVES The aim was to determine the risk and burden of lung cancer in patients with IPF, accounting for known confounders. METHODS We conducted a comprehensive literature search of MEDLINE, EMBASE and SCOPUS databases and used the Newman-Castle Ottawa criteria to assess study quality. We then assessed the quality of ascertainment of IPF cases based on modern consensus criteria. Data that relied on administrative claims or autopsies were excluded. We calculated summary risk estimates using a random effects model. RESULTS Twenty-six cohort studies were included in the final analysis. The estimated adjusted incidence rate ratio (IRR) from 2 studies was 6.42 (95% confidence interval (CI): 3.21-9.62) and accounted for age, gender and smoking. The summary incidence rate from 12 studies was 1.84 per 100 person-years (95% CI: 1.33-2.36), which was similar to the summary mortality rate of 1.27 per 100 person-years (95% CI: 0.66-1.89) obtained from 4 studies. The summary prevalence from 10 studies was 13.74% (95% CI: 10.17-17.30), and the proportion of deaths attributable to lung cancer was 10.20 (95% CI: 8.52-11.87) and was obtained from 9 studies. CONCLUSION IPF is an increased independent risk factor for lung cancer, even after accounting for smoking. Further well-designed studies using modern consensus criteria are needed to explore mechanisms of this association.

[1]  M. YektaKooshali,et al.  Lung cancer in idiopathic pulmonary fibrosis: A systematic review and meta-analysis , 2018, PloS one.

[2]  Yanhong Ren,et al.  Incidence and radiologic‐pathological features of lung cancer in idiopathic pulmonary fibrosis , 2018, The clinical respiratory journal.

[3]  A. Gemma,et al.  Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone. , 2018, Respiratory investigation.

[4]  S. Matsuda,et al.  Respiratory comorbidities and risk of mortality in hospitalized patients with idiopathic pulmonary fibrosis. , 2018, Respiratory investigation.

[5]  Ruchi Bansal,et al.  Drug targeting to myofibroblasts: Implications for fibrosis and cancer , 2017, Advanced drug delivery reviews.

[6]  Demosthenes Bouros,et al.  Diagnosis of Idiopathic Pulmonary Fibrosis “Pragmatic Challenges in Clinical Practice” , 2017, Front. Med..

[7]  Hanna M. Nurmi,et al.  Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis , 2017, Respiratory Research.

[8]  Vasilis Aidinis,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis. , 2017, Pulmonary pharmacology & therapeutics.

[9]  J. Ruiz-manzano,et al.  Lung Cancer in Patients With Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis. A Descriptive Study in a Spanish Series. , 2017, Archivos de bronconeumologia.

[10]  H. Collard,et al.  Code‐based Diagnostic Algorithms for Idiopathic Pulmonary Fibrosis. Case Validation and Improvement , 2017, Annals of the American Thoracic Society.

[11]  H. Asamura,et al.  Clinicopathological, Immunohistochemical, and Genetic Features of Primary Lung Adenocarcinoma Occurring in the Setting of Usual Interstitial Pneumonia Pattern , 2016, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  M. Tanahashi,et al.  Distinctive impact of pre-existing interstitial lung disease on the risk of chemotherapy-related lung injury in patients with lung cancer , 2016, Cancer Chemotherapy and Pharmacology.

[13]  A. Warth,et al.  Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis , 2016, PloS one.

[14]  Asger Dirksen,et al.  Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling. , 2016, American journal of respiratory and critical care medicine.

[15]  S. Nathan,et al.  Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation. , 2015, American journal of respiratory and critical care medicine.

[16]  C. Vancheri,et al.  Idiopathic pulmonary fibrosis and lung cancer: a clinical and pathogenesis update , 2015, Current opinion in pulmonary medicine.

[17]  N. Inui,et al.  Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer , 2015, PloS one.

[18]  G. Raghu,et al.  Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review , 2015, European Respiratory Journal.

[19]  K. Yoh,et al.  Efficacy and Safety of Combined Carboplatin, Paclitaxel, and Bevacizumab for Patients with Advanced Non-squamous Non-small Cell Lung Cancer with Pre-existing Interstitial Lung Disease: A Retrospective Multi-institutional Study. , 2015, Anticancer research.

[20]  J. Yim,et al.  Validation of the GAP score in Korean patients with idiopathic pulmonary fibrosis. , 2015, Chest.

[21]  V. Poletti,et al.  The impact of lung cancer on survival of idiopathic pulmonary fibrosis. , 2015, Chest.

[22]  R. Sussman,et al.  A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. , 2014, The New England journal of medicine.

[23]  H. Collard,et al.  Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. , 2014, The New England journal of medicine.

[24]  O. Hilberg,et al.  How does comorbidity influence survival in idiopathic pulmonary fibrosis? , 2014, Respiratory Medicine.

[25]  C. Park,et al.  Lung cancer risk among patients with combined pulmonary fibrosis and emphysema. , 2014, Respiratory medicine.

[26]  Jae Ho Lee,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis: clinical characteristics and impact on survival. , 2013, Respiratory medicine.

[27]  Carlo Vancheri,et al.  Common pathways in idiopathic pulmonary fibrosis and cancer , 2013, European Respiratory Review.

[28]  Ping Li,et al.  Serum miR-21 and miR-155 expression in idiopathic pulmonary fibrosis , 2013, The Journal of asthma : official journal of the Association for the Care of Asthma.

[29]  M. Mascalchi,et al.  Four-Year Results of Low-Dose CT Screening and Nodule Management in the ITALUNG Trial , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[30]  T. Higami,et al.  Surgical treatment for primary lung cancer combined with idiopathic pulmonary fibrosis , 2013, General Thoracic and Cardiovascular Surgery.

[31]  Luba Nalysnyk,et al.  Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature , 2012, European Respiratory Review.

[32]  Y. Kondoh,et al.  Efficacy of Chemotherapy for Advanced Non-Small Cell Lung Cancer with Idiopathic Pulmonary Fibrosis , 2012, Respiration.

[33]  Ugo Pastorino,et al.  Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial , 2012, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[34]  Choon-Sik Park,et al.  Prevalence, risk factors and survival of lung cancer in the idiopathic pulmonary fibrosis , 2012, Thoracic Cancer.

[35]  Li Zhang,et al.  Clinical characteristics of patients with lung cancer and idiopathic pulmonary fibrosis in China , 2011, Thoracic cancer.

[36]  Y. Kawabata,et al.  Survival after surgery for pathologic stage IA non-small cell lung cancer associated with idiopathic pulmonary fibrosis. , 2011, The Annals of thoracic surgery.

[37]  Luca Richeldi,et al.  Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. , 2011, The New England journal of medicine.

[38]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[39]  S. Sahn,et al.  Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials , 2011, The Lancet.

[40]  Takeshi Johkoh,et al.  American Thoracic Society Documents An Official ATS / ERS / JRS / ALAT Statement : Idiopathic Pulmonary Fibrosis : Evidence-based Guidelines for Diagnosis and Management , 2011 .

[41]  D. Schroeder,et al.  Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. , 2010, Chest.

[42]  I. D. Johnston,et al.  Cryptogenic fibrosing alveolitis and lung cancer: the BTS study , 2009, Thorax.

[43]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[44]  K. Chida,et al.  Cumulative incidence of and predictive factors for lung cancer in IPF , 2009, Respirology.

[45]  R. Hubbard,et al.  The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK. , 2007, Respiratory medicine.

[46]  M. Mishima,et al.  Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. , 2007, Chest.

[47]  J. Hagood,et al.  Enhanced myofibroblastic differentiation and survival in Thy-1(-) lung fibroblasts. , 2007, American journal of respiratory cell and molecular biology.

[48]  P. Brennan,et al.  High cumulative risk of lung cancer death among smokers and nonsmokers in Central and Eastern Europe. , 2006, American journal of epidemiology.

[49]  M. Chung,et al.  Prognostic factors and causes of death in Korean patients with idiopathic pulmonary fibrosis. , 2006, Respiratory medicine.

[50]  S. Kudoh,et al.  Occupational and Environmental Factors and Idiopathic Pulmonary Fibrosis in Japan , 2005 .

[51]  John Connett,et al.  The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality , 2005, Annals of Internal Medicine.

[52]  M. Sawabe,et al.  A clinical study of idiopathic pulmonary fibrosis based on autopsy studies in elderly patients. , 2003, Internal medicine.

[53]  S. Sakai,et al.  Lung Cancer Associated With Diffuse Pulmonary Fibrosis: CT–Pathologic Correlation , 2003, Journal of thoracic imaging.

[54]  F. Martinez,et al.  Radiological versus histological diagnosis in UIP and NSIP: survival implications , 2003, Thorax.

[55]  V. Pankratz,et al.  Primary pulmonary carcinoma in patients with idiopathic pulmonary fibrosis. , 2002, Mayo Clinic proceedings.

[56]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[57]  T. Kuroki,et al.  Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis , 2002, Virchows Archiv.

[58]  T. Shim,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis. , 2001, The European respiratory journal.

[59]  Richard Doll,et al.  Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies , 2000, BMJ : British Medical Journal.

[60]  R. Hubbard,et al.  Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. , 2000, American journal of respiratory and critical care medicine.

[61]  David A. Lynch,et al.  Idiopathic pulmonary fibrosis: Diagnosis and treatment: International Consensus Statement , 2000 .

[62]  M. Fukayama,et al.  Pulmonary fibrosis and lung carcinoma: A comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma , 1999, Pathology international.

[63]  M. Kitaichi,et al.  Hospital-based historical cohort study of 234 histologically proven Japanese patients with IPF. , 1999, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[64]  J. M. Harris,et al.  Does cryptogenic fibrosing alveolitis carry an increased risk of death from lung cancer? , 1998, Journal of epidemiology and community health.

[65]  J A Waldron,et al.  Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. , 1997, American journal of respiratory and critical care medicine.

[66]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[67]  J. Im,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis: CT findings. , 1996, Journal of computer assisted tomography.

[68]  D. Mannino,et al.  Pulmonary Fibrosis and Lung Cancer in the United States: Analysis of the Multiple Cause of Death Mortality Data, 1979 Through 1991 , 1996, Southern medical journal.

[69]  M. Hara,et al.  Iung cancer associated with usual interstitial pneumonia , 1995, Pathology international.

[70]  A. Nagai,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis. , 1992, The Tohoku journal of experimental medicine.

[71]  A Whitehead,et al.  A general parametric approach to the meta-analysis of randomized clinical trials. , 1991, Statistics in medicine.

[72]  M. Lebowitz,et al.  Cryptogenic fibrosing alveolitis and lung cancer. , 1980, Thorax.