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CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer

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Abstract

Objectives

To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer.

Methods

Patients undergoing chest CT and testing for the above gene mutations were included. Qualitative evaluation of CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity; density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis; nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction; location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion. Statistical analysis was performed to assess association of features with each gene mutation. ROC curves for gene mutations were drawn; the corresponding area under the curve was calculated. P-values <0.05 were considered significant.

Results

Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation; 31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR mutation was associated with air bronchogram, pleural retraction, females, non-smokers, small lesion size, and absence of fibrosis. ALK rearrangements were associated with age and pleural effusion. KRAS mutation was associated with round shape, nodules in non-tumour lobes, and smoking.

Conclusions

This study disclosed associations between CT features and alterations of EGFR (air bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes).

Key Points

• Air bronchogram, pleural retraction, small size relate to EGFR mutation in NSCLC.

• Pleural effusion and younger age relate to ALK mutation.

• Round lesion shape, nodules in non-tumour lobes relate to KRAS mutation.

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References

  1. Buettner R, Wolf J, Thomas RK (2013) Lessons learned from lung cancer genomics: the emerging concept of individualized diagnostics and treatment. J Clin Oncol 31(15):1858–1865

    Article  CAS  PubMed  Google Scholar 

  2. Jorge SE, Kobayashi SS, Costa DB (2014) Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data. Braz J Med Biol Res 47(11):929–933

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Kwak EL, Bang YJ, Ross D et al (2010) Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med 363:1693

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Shaw AT, Kim DW, Mehra R et al (2014) Ceritinib in ALK-rearranged non–small-cell lung cancer. N Engl J Med 370:1189–1197

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Seto T, Kiura K, Nishio M et al (2013) CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study. Lancet Oncol 14:590–598

    Article  CAS  PubMed  Google Scholar 

  6. Rodenhuis S, Slebos RJ (1992) Clinical significance of ras oncogene activation in human lung cancer. Cancer Res 52:2665–2669s

    Google Scholar 

  7. Gerber DE, Gandhi L, Costa DB (2014) Management and future directions in non-small cell lung cancer with known activating mutations. Am Soc Clin Oncol Educ Book 34:e353–e365

    Article  Google Scholar 

  8. Colen R, Foster I, Gatenby R et al (2014) NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures. Transl Oncol 24(7(5)):556–569

    Article  Google Scholar 

  9. Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892

    Article  CAS  PubMed  Google Scholar 

  10. Kuo MD, Jamshidi N (2014) Behind the numbers: Decoding molecular phenotypes with radiogenomics–guiding principles and technical considerations. Radiology 270(2):320–325

    Article  PubMed  Google Scholar 

  11. Rutman AM, Kuo MD (2009) Radiogenomics: creating a link between molecular diagnostics and diagnostic imaging. Eur J Radiol 70(2):232–241

    Article  PubMed  Google Scholar 

  12. Hsu JS, Huang MS, Chen CY et al (2014) Correlation between EGFR mutation status and computed tomography features in patients with advanced pulmonary adenocarcinoma. J Thorac Imaging 29:357–363

    Article  PubMed  Google Scholar 

  13. Gevaert O, Xu J, Hoang CD et al (2012) Non-small cell lung cancer: identifying prognostic imaging biomarkers by leveraging public gene expression microarray data–methods and preliminary results. Radiology 264(2):387–396

    Article  PubMed Central  PubMed  Google Scholar 

  14. Yamamoto S, Korn RL, Oklu R et al (2014) ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization. Radiology 272(2):568–576

    Article  PubMed  Google Scholar 

  15. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC (eds) (2004) Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARCPress, Lyon

    Google Scholar 

  16. Kundel HL, Polansky M (2003) Measurement of observer agreement. Radiology 228:303–308

    Article  PubMed  Google Scholar 

  17. Jain R, Poisson L, Gutman D et al (2014) Outcome prediction in patients with glioblastoma using imaging, clinical and genomic biomarkers: focus on the non-enhancing component of the tumor. Radiology 272(2):484–493

    Article  PubMed Central  PubMed  Google Scholar 

  18. I-SPY 2 Trial. Accessed at: http://www.ispy2trial.org/about/i-spy-2-trial; 2014

  19. Karlo CA, Di Paolo PL, Chaim J et al (2013) Radiogenomics of Clear Cell Renal Cell Carcinoma: Associations between CT Imaging Features and Mutations. Radiology 270(2):464–471

    Article  PubMed Central  PubMed  Google Scholar 

  20. Cooke SL, Ng CK, Melnyk N et al (2010) Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. Oncogene 29(35):4905–4913

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  CAS  PubMed  Google Scholar 

  22. Dacic S (2013) Molecular genetic testing for lung adenocarcinomas: a practical approach to clinically relevant mutations and translocations. J Clin Pathol 66(10):870–874

    Article  CAS  PubMed  Google Scholar 

  23. Dacic S, Shuai Y, Yousem S et al (2010) Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas. Mod Pathol 23:159–168

    Article  CAS  PubMed  Google Scholar 

  24. Chang YL, Lin MW, Shih JY, Wu CT, Lee YC (2012) The significance of visceral pleural surface invasion in 321 cases of non-small cell lung cancers with pleural retraction. Ann Surg Oncol 19(9):3057–3064

    Article  PubMed  Google Scholar 

  25. Yoshino I, Nakanishi R, Kodate M et al (2000) Pleural retraction and intra-tumoral air-bronchogram as prognostic factors for stage I pulmonary adenocarcinoma following complete resection. Int Surg 85(2):105–112

    CAS  PubMed  Google Scholar 

  26. Toh CK, Gao F, Lim WT et al (2006) Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol 24(15):2245–2251

    Article  PubMed  Google Scholar 

  27. Nakada T, Okumura S, Kuroda H, et al (2014) Imaging Characteristics in ALK Fusion-Positive Lung Adenocarcinomas by Using HRCT. Ann Thorac Cardiovasc Surg. Jun 3. [Epub ahead of print]

  28. Martin P, Leighl NB, Tsao MS, Shepherd FA (2013) KRAS mutations as prognostic and predictive markers in non-small cell lung cancer. J Thorac Oncol 8(5):530–542

    CAS  PubMed  Google Scholar 

  29. Slebos RJ, Kibbelaar RE, Dalesio O et al (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323:561–565

    Article  CAS  PubMed  Google Scholar 

  30. Linardou H, Dahabreh IJ, Kanaloupiti D et al (2008) Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFRtargeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9:962–972

    Article  CAS  PubMed  Google Scholar 

  31. Mao C, Qiu LX, Liao RY et al (2010) KRAS mutations and resistance to EGFRTKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies. Lung Cancer 69:272–278

    Article  PubMed  Google Scholar 

  32. Ruppert AM, Lerolle U, Carette MF et al (2011) Coexisting pulmonary nodules in operable lung cancer: prevalence and probability of malignancy. Lung Cancer 74(2):233–238

    Article  CAS  PubMed  Google Scholar 

  33. Riely GJ, Kris MG, Rosenbaum D et al (2008) Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res 14:5731–5734

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Ou SH (2013) Lung cancer in never-smokers. Does smoking history matter in the era of molecular diagnostics and targeted therapy? J Clin Pathol 66(10):839–846

    Article  PubMed  Google Scholar 

  35. Lee HJ, Kim YT, Kang CH et al (2013) Epidermal growth factor receptor mutation in lung adenocarcinomas: relationship with CT characteristics and histologic subtypes. Radiology 268(1):254–264

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The English text has been revised by Anne Prudence Collins (Editor and Translator Medical &Scientific Publications; Member AITI - FIT UNESCO; Member ASSOINTERPRETI).The data have been managed by Cristiana Fodor, data manager at Department of Radiotherapy, European Institute of Oncology, Milan (IT).

The scientific guarantor of this publication is Massimo Bellomi. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.The authors state that this work has not received any funding. Sara Raimondi (one of the authors) is a statistician who kindly provided statistical advice for this manuscript. Institutional Review Board approval was not required because in this retrospective analysis all the patients had signed an informed consent to the use of clinical and imaging data for scientific and/or educational purposes. Written informed consent was obtained from all subjects (patients) in this study. Methodology: observational study, performed at one institution.

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Authors and Affiliations

  1. Department of Radiology, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

    Stefania Rizzo, Cristiano Rampinelli & Massimo Bellomi

  2. Department of Thoracic Surgery, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

    Francesco Petrella & Lorenzo Spaggiari

  3. Department of Health Sciences, University of Milan, via A. di Rudinì 8, 20142, Milan, Italy

    Valentina Buscarino, Federica De Maria & Massimo Bellomi

  4. Department of Epidemiology and Biostatistics, European Institute of Oncology, via Ramusio, 1, 20141, Milan, Italy

    Sara Raimondi

  5. Department of Pathology, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

    Massimo Barberis & Caterina Fumagalli

  6. Department of Thoracic Oncology, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

    Gianluca Spitaleri & Filippo De Marinis

Authors
  1. Stefania Rizzo
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  2. Francesco Petrella
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  3. Valentina Buscarino
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  4. Federica De Maria
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  12. Massimo Bellomi
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Correspondence to Stefania Rizzo.

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Rizzo, S., Petrella, F., Buscarino, V. et al. CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer. Eur Radiol 26, 32–42 (2016). https://doi.org/10.1007/s00330-015-3814-0

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  • DOI: https://doi.org/10.1007/s00330-015-3814-0

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