Epidermal Growth Factor Receptor Mutations: Effect on Volume Doubling Time of Non–Small-Cell Lung Cancer Patients

Background: The purpose of this study was to retrospectively compare the volume doubling time (VDT) on serial computed tomography (CT) of non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation with that of NSCLC without the mutation. Methods: One hundred and two pathologically proven NSCLCs, including 69 patients with lung adenocarcinoma, were reviewed with helical CT. Each tumor underwent at least two CT scans. The VDT was calculated using a modified Schwartz formula. EGFR mutations at exons 18–21 were determined by common fragment analysis and Cycleave method. Result: The median VDT of all the patients was 188 days. EGFR mutations were noted in 35 of the 102 patients. The VDT in the 35 patients with EGFR mutations (median 676 days) was longer than that in the 67 patients without EGFR mutations (median 139 days) (p <0.001). By histology subtype, the VDT of adenocarcinoma (305 days) was longer than that of squamous cell carcinoma (81 days) and other types (90 days; p <0.001). Conclusion: In NSCLC patients, positive EGFR mutation status may be associated with longer VDT, which seemed to have a slowly progressive and less-aggressive character. More accurate evaluation of VDT may be helpful for understanding the natural history of EGFR mutation–positive NSCLC and treatment with EGFR tyrosine kinase inhibitors.

[1]  [Management of solitary pulmonary nodules]. , 2015, MMW Fortschritte der Medizin.

[2]  Ying Wang,et al.  Smooth or attached solid indeterminate nodules detected at baseline CT screening in the NELSON study: cancer risk during 1 year of follow-up. , 2009, Radiology.

[3]  Iwao Yamaguchi,et al.  Volume doubling time of lung cancers detected in a chest radiograph mass screening program: Comparison with CT screening. , 2012, Oncology letters.

[4]  Masaki Hara,et al.  Epidermal Growth Factor Receptor Gene Mutation and Computed Tomographic Findings in Peripheral Pulmonary Adenocarcinoma , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[5]  K. Matsuo,et al.  Prospective Validation for Prediction of Gefitinib Sensitivity by Epidermal Growth Factor Receptor Gene Mutation in Patients with Non-Small Cell Lung Cancer , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  R. Warren,et al.  BRCA1 Mutation and Young Age Predict Fast Breast Cancer Growth in the Dutch, United Kingdom, and Canadian Magnetic Resonance Imaging Screening Trials , 2007, Clinical Cancer Research.

[7]  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.

[8]  Elisabeth Brambilla,et al.  The 2004 World Health Organization classification of lung tumors. , 2005, Seminars in roentgenology.

[9]  A. Dirksen,et al.  Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning , 2010, Thorax.

[10]  Y. Yatabe,et al.  Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer , 2007, Cancer science.

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

[12]  H Nakata,et al.  Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time. , 2000, AJR. American journal of roentgenology.

[13]  D. Xu,et al.  Nodule management protocol of the NELSON randomised lung cancer screening trial. , 2006, Lung cancer.

[14]  S Sone,et al.  Growth rate of small lung cancers detected on mass CT screening. , 2000, The British journal of radiology.

[15]  Mordecai Schwartz A biomathematical approach to clinical tumor growth , 1961, Cancer.

[16]  A. Sakurada,et al.  Tumor doubling time and prognostic assessment of patients with primary lung cancer , 1994, Cancer.

[17]  Yih-Leong Chang,et al.  Frequent EGFR mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis , 2012, European Respiratory Journal.

[18]  Takashi Ogura,et al.  Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features. , 2012, Lung Cancer.

[19]  Dawei Yang Estimating overdiagnosis in low-dose computed tomography screening for lung cancer : a cohort study , 2013 .

[20]  Chien-Jen Chen,et al.  Epidermal Growth Factor Receptor Mutation Status in Stage I Lung Adenocarcinoma with Different Image Patterns , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[21]  F. Detterbeck,et al.  Turning Gray: The Natural History of Lung Cancer Over Time , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[22]  Kenji Suzuki,et al.  Molecular markers and changes of computed tomography appearance in lung adenocarcinoma with ground-glass opacity. , 2007, Japanese journal of clinical oncology.

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

[24]  Rebecca M. Lindell,et al.  Five-year lung cancer screening experience: CT appearance, growth rate, location, and histologic features of 61 lung cancers. , 2007, Radiology.

[25]  Michelle S. Ginsberg,et al.  Are There Imaging Characteristics Associated with Epidermal Growth Factor Receptor and KRAS Mutations in Patients with Adenocarcinoma of the Lung with Bronchioloalveolar Features? , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[26]  P. Buell,et al.  Asymptomatic solitary pulmonary nodules. Host survival, tumor size, and growth rate. , 1973, The Journal of thoracic and cardiovascular surgery.