Frequent EGFR mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis

Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor (EGFR) mutation rate of NSCLC patients with MIPC at initial diagnosis. From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysed EGFR mutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested for EGFR mutations from April 2001 to November 2008. From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detect EGFR mutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higher EGFR mutation rate (p=0.036); even male smokers had a high EGFR mutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and having EGFR mutation were associated with longer overall survival. NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma and EGFR mutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.

[1]  A. Jemal,et al.  Cancer statistics, 2011 , 2011, CA: a cancer journal for clinicians.

[2]  Thomas J. Smith,et al.  American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  William Pao,et al.  Comprehensive Histologic Assessment Helps to Differentiate Multiple Lung Primary Nonsmall Cell Carcinomas From Metastases , 2009, The American journal of surgical pathology.

[4]  J. Abbruzzese,et al.  F1000 highlights , 2009, JAMA.

[5]  J. Shih,et al.  Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  T. Colby,et al.  Chest pain and progressive miliary infiltrates in an elderly man. , 2009, Chest.

[7]  J. Shih,et al.  First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer. , 2008, American journal of respiratory and critical care medicine.

[8]  J. Shih,et al.  Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma , 2008, European Respiratory Journal.

[9]  Yih-Leong Chang,et al.  Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Mutations Is Associated with Poor Gefitinib Treatment Response , 2008, Clinical Cancer Research.

[10]  N. Müller,et al.  Fleischner Society: glossary of terms for thoracic imaging. , 2008, Radiology.

[11]  Susan T. Stewart,et al.  The value of medical interventions for lung cancer in the elderly , 2007, Cancer.

[12]  J. Crowley,et al.  The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[13]  Daniel A. Haber,et al.  Epidermal growth factor receptor mutations in lung cancer , 2007, Nature Reviews Cancer.

[14]  Y. Ogawa,et al.  Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts gefitinib response in association with epidermal growth factor receptor mutations. , 2006, Anticancer research.

[15]  J. Minna,et al.  Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. , 2006, Journal of the National Cancer Institute.

[16]  Yih-Leong Chang,et al.  Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer , 2006, International journal of cancer.

[17]  J. Ferlay,et al.  Global Cancer Statistics, 2002 , 2005, CA: a cancer journal for clinicians.

[18]  Takayuki Kosaka,et al.  Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer , 2004, Cancer Research.

[19]  Elisabeth Brambilla,et al.  Pathology and genetics of tumours of the lung , pleura, thymus and heart , 2004 .

[20]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[21]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[22]  Nicola Sverzellati,et al.  Diagnostic Imaging of Diffuse Infiltrative Disease of the Lung , 2004, Respiration.

[23]  D. Wooff Logistic Regression: a Self-learning Text, 2nd edn , 2004 .

[24]  David Cella,et al.  Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. , 2003, JAMA.

[25]  Masahiro Fukuoka,et al.  Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  G. Chang,et al.  Successful treatment of multifocal bronchioloalveolar cell carcinoma with ZD1839 (Iressa) in two patients. , 2003, Journal of the Formosan Medical Association = Taiwan yi zhi.

[27]  Matthias Schroder,et al.  Logistic Regression: A Self-Learning Text , 2003 .

[28]  E. Pallisa,et al.  Miliary lung disease revisited. , 2002, Current problems in diagnostic radiology.

[29]  S. Swensen,et al.  Radiologic findings of bronchogenic carcinoma with pulmonary metastases at presentation. , 1999, Clinical radiology.

[30]  S. Broste,et al.  The changing radiographic presentation of bronchogenic carcinoma with reference to cell types. , 1996, Chest.

[31]  Yung‐Chie Lee,et al.  Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer. , 1995, American journal of respiratory and critical care medicine.

[32]  S. Umeki Association of miliary lung metastases and bone metastases in bronchogenic carcinoma. , 1993, Chest.

[33]  D. Hosmer,et al.  Applied Logistic Regression , 1991 .

[34]  L. Coppage,et al.  Metastatic disease to the chest in patients with extrathoracic malignancy , 1987, Journal of thoracic imaging.

[35]  R. Kucherlapati,et al.  Genetic analysis of epidermal growth factor action: assignment of human epidermal growth factor receptor gene to chromosome 7. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Sauter,et al.  Miliary never-smoking adenocarcinoma of the lung: strong association with epidermal growth factor receptor exon 19 deletion. , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[37]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[38]  Lin Huan,et al.  Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer , 2010 .

[39]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[40]  H. Ohmatsu,et al.  Association of multiple pulmonary metastases with response to gefitinib in patients with non-small cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  K S Lee,et al.  Diffuse micronodular lung disease: HRCT and pathologic findings. , 1999, Journal of computer assisted tomography.

[42]  H. Hansen,et al.  Lung cancer. , 1990, Cancer chemotherapy and biological response modifiers.