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Synchronous Non-small Cell Lung Cancers: Diagnostic Yield can be Improved by Histologic and Genetic Methods

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Current criteria for identification of synchronous non-small cell lung cancers (NSCLCs) may be confusing in patients with lymphatic metastases. This study was aimed at investigating the strategy using both the new histologic classification and driver-mutational testing to define multiple primary lung cancers.

Methods

Prospectively collected data of surgical patients with synchronous NSCLCs were retrospectively analyzed. Cases were defined using the Martini–Melamed criteria, and validated by histologic subtyping based on the new classification and driver mutation of selected genes. Survival was estimated between patients with multiple primary and metastatic disease controlling by nodal (N) stage. Factors associated with prolonged survival were evaluated using the Cox proportional hazards mode.

Results

A total of 131 patients followed for at least 12 months were included in this study. Controlling by N0 stage, patients who were diagnosed with multiple primary NSCLCs showed better relapse-free survival (RFS) than those with intrapulmonary metastases categorized either by the Martini–Melamed criteria or by histologic-mutational methods (both p < 0.0001). However, at N+ stage, patients stratified by Martini–Melamed criteria showed no difference in survival (p = 0.517), while those defined by histologic-mutational methods maintained superior survival compared with the control group (p = 0.042). On multivariate analysis, only N0 and diagnosis of independent lung lesions by histologic-mutational methods were significant predictors of better RFS (p = 0.031 and 0.001, respectively)

Conclusions

The histologic-mutational strategy may be an option for identification of synchronous NSCLC when traditional criteria were not applicable, especially in cases with positive lymphatics. N0 stage and the diagnosis of independent pulmonary tumors were associated with better RFS.

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References

  1. Gazdar AF, Minna JD. Multifocal lung cancers: clonality vs field cancerization and does it matter? J Natl Cancer Inst. 2009;101(8):541–3.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Flieder DB, Vazquez M, Carter D, et al. Pathologic findings of lung tumors diagnosed on baseline CT screening. Am J Surg Pathol. 2006;30(5):606–13.

    Article  PubMed  Google Scholar 

  3. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70(4):606–12.

    CAS  PubMed  Google Scholar 

  4. Tanvetyanon T, Finley DJ, Fabian T, et al. Prognostic factors for survival after complete resections of synchronous lung cancers in multiple lobes: pooled analysis based on individual patient data. Ann Oncol. 2013;24(4):889–94.

    Article  CAS  PubMed  Google Scholar 

  5. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.

    Article  PubMed  Google Scholar 

  6. Sun Y, Ren Y, Fang Z, et al. Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol. 2010;28(30):4616–20.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Li C, Fang R, Sun Y, et al. Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers. PLoS One. 2011;6(11):e28204.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Girard N, Deshpande C, Lau C, et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol. 2009;33(12):1752–64.

    Article  PubMed  Google Scholar 

  9. Chapman AD, Kerr KM. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer. 2000;83(5):632–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kitamura H, Okudela K. Bronchioloalveolar neoplasia. Int J Clin Exp Pathol. 2010;4(1):97–9.

    PubMed Central  PubMed  Google Scholar 

  11. Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012;30(35):4352–9.

    Article  CAS  PubMed  Google Scholar 

  12. Kozower BD, Larner JM, Detterbeck FC, et al. Special treatment issues in non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e369S–99S.

    Article  PubMed  Google Scholar 

  13. Trousse D, Barlesi F, Loundou A, et al. Synchronous multiple primary lung cancer: an increasing clinical occurrence requiring multidisciplinary management. J Thorac Cardiovasc Surg. 2007;133(5):1193–200.

    Article  PubMed  Google Scholar 

  14. Flieder DB. Commonly encountered difficulties in pathologic staging of lung cancer. Arch Pathol Lab Med. 2007;131(7):1016–26.

    PubMed  Google Scholar 

  15. Nakata M, Sawada S, Yamashita M, et al. Surgical treatments for multiple primary adenocarcinoma of the lung. Ann Thorac Surg. 2004;78(4):1194–9.

    Article  PubMed  Google Scholar 

  16. Tsunezuka Y, Matsumoto I, Tamura M, et al. The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre. Eur J Surg Oncol. 2004;30(7):781–5.

    Article  CAS  PubMed  Google Scholar 

  17. De Leyn P, Moons J, Vansteenkiste J, et al. Survival after resection of synchronous bilateral lung cancer. Eur J Cardiothorac Surg. 2008;34(6):1215–22.

    Article  PubMed  Google Scholar 

  18. Finley DJ, Yoshizawa A, Travis W, et al. Predictors of outcomes after surgical treatment of synchronous primary lung cancers. J Thorac Oncol. 2010;5(2):197–205.

    Article  PubMed  Google Scholar 

  19. Fabian T, Bryant AS, Mouhlas AL, et al. Survival after resection of synchronous non-small cell lung cancer. J Thorac Cardiovasc Surg. 2011;142(3):547–53.

    Article  PubMed  Google Scholar 

  20. Shah AA, Barfield ME, Kelsey CR, et al. Outcomes after surgical management of synchronous bilateral primary lung cancers. Ann Thorac Surg. 2012;93(4):1055–60; discussion 1060.

  21. Dumont P, Gasser B, Rouge C, et al. Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients. Chest. 1998;113(2):391–5.

    Article  CAS  PubMed  Google Scholar 

  22. Li ZH, Zheng J, Weiss LM, et al. c-k-ras and p53 mutations occur very early in adenocarcinoma of the lung. Am J Pathol. 1994;144(2):303–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Sartori G, Cavazza A, Bertolini F, et al. A subset of lung adenocarcinomas and atypical adenomatous hyperplasia-associated foci are genotypically related: an EGFR, HER2, and K-ras mutational analysis. Am J Clin Pathol. 2008;129(2):202–10.

    Article  CAS  PubMed  Google Scholar 

  24. Yatabe Y, Matsuo K, Mitsudomi T. Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol. 2011;29(22):2972–7.

    Article  CAS  PubMed  Google Scholar 

  25. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519–25.

    Article  Google Scholar 

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Conflicts of Interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Yiliang Zhang MD, Haichuan Hu MD, Rui Wang PhD, Ting Ye MD, Yunjian Pan MD, Lei Wang MD, Yang Zhang MD, Hang Li MD, Yihua Sun PhD & Haiquan Chen MD

  2. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Yuan Li PhD & Lei Shen MD

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Yiliang Zhang MD, Haichuan Hu MD, Rui Wang PhD, Ting Ye MD, Yunjian Pan MD, Lei Wang MD, Yang Zhang MD, Hang Li MD, Yuan Li PhD, Lei Shen MD, Yihua Sun PhD & Haiquan Chen MD

  4. Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark

    Yongfu Yu MD

  5. University of Colorado Comprehensive Cancer Center, Aurora, CO, USA

    David Garfield MD

Authors
  1. Yiliang Zhang MD
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  2. Haichuan Hu MD
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  3. Rui Wang PhD
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  4. Ting Ye MD
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  5. Yunjian Pan MD
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  6. Lei Wang MD
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  7. Yang Zhang MD
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  8. Hang Li MD
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  9. Yuan Li PhD
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  10. Lei Shen MD
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  11. Yongfu Yu MD
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  12. Yihua Sun PhD
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  13. Haiquan Chen MD
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  14. David Garfield MD
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Corresponding authors

Correspondence to Yihua Sun PhD or Haiquan Chen MD.

Additional information

Yiliang Zhang and Haichuan Hu have contributed equally to this study and both should be considered as first author.

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Cite this article

Zhang, Y., Hu, H., Wang, R. et al. Synchronous Non-small Cell Lung Cancers: Diagnostic Yield can be Improved by Histologic and Genetic Methods. Ann Surg Oncol 21, 4369–4374 (2014). https://doi.org/10.1245/s10434-014-3840-1

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  • DOI: https://doi.org/10.1245/s10434-014-3840-1

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