Advertisement

Annals of Nuclear Medicine

, Volume 33, Issue 2, pp 93–102 | Cite as

18F-fluorodeoxyglucose positron emission tomography is correlated with the pathological necrosis and decreased microvessel density in lung adenocarcinomas

  • Young Wha Koh
  • Su Jin LeeEmail author
  • Seong Yong ParkEmail author
Original Article

Abstract

Objective

We explored the relationship between preoperative 18F-FDG-PET parameters, tumor necrosis, and microvessel density (MVD) in patients with pulmonary adenocarcinomas.

Methods

A total of 164 patients, who underwent surgical resection for lung adenocarcinoma, were reviewed retrospectively. The maximum standardized uptake value (SUVmax), peak SUV corrected for lean body mass (SULpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values were measured by preoperative 18F-FDG-PET. The extent of tumor necrosis was examined and CD31 expression was evaluated to count the MVD.

Results

The SUVmax, SULpeak, MTV, and TLG levels were significantly lower in patients exhibiting no necrosis compared to those with necrosis. When we divided the patients into two groups based on high vs. low PET parameter values, elevated SUVmax, SULpeak, MTV, and TLG values were significantly more associated with partial or diffuse necrosis than were lower values (p < 0.001). A negative correlation was evident between the MVD and SUVmax, MVD and SULpeak, MVD and MTV, and MVD and TLG. Tumor necrosis was correlated with a shorter overall survival (OS) (p = 0.007) and recur-free survival (RFS) (p < 0.001). However, multivariate analysis revealed that necrosis was not of prognostic significance. The SUVmax, MTV and TLG were associated with inferior OS or RFS rates in univariate analysis, however, not in multivariate analysis.

Conclusion

High-level FDG accumulation is correlated with tumor necrosis in lung adenocarcinoma.

Keywords

Lung adenocarcinoma Positron emission tomography Necrosis Hypoxia Prognosis 

Notes

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (NRF-2017R1C1B5076342 for Young Wha Koh and NRF-2016R1C1B2011583 for Su Jin Lee) and by the New Faculty Research Fund of Ajou University School of Medicine to Young Wha Koh.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26:225–39.CrossRefGoogle Scholar
  2. 2.
    Park SY, Lee HS, Jang HJ, Lee GK, Chung KY, Zo JI. Tumor necrosis as a prognostic factor for stage IA non-small cell lung cancer. Ann Thorac Surg. 2011;91:1668–73.CrossRefGoogle Scholar
  3. 3.
    Shahab I, Fraire AE, Greenberg SD, Johnson EH, Langston C, Roggli VL. Morphometric quantitation of tumor necrosis in stage 1 non-small cell carcinoma of lung: prognostic implications. Mod Pathol. 1992;5:521–4.Google Scholar
  4. 4.
    Berghoff AS, Ilhan-Mutlu A, Wohrer A, Hackl M, Widhalm G, Hainfellner JA, et al. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases. Strahlenther Onkol. 2014;190:676–85.CrossRefGoogle Scholar
  5. 5.
    Giatromanolaki A, Koukourakis M, O’Byrne K, Fox S, Whitehouse R, Talbot DC, et al. Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol. 1996;179:80–8.CrossRefGoogle Scholar
  6. 6.
    Burger IA, Casanova R, Steiger S, Husmann L, Stolzmann P, Huellner MW, et al. 18F-FDG PET/CT of non-small cell lung carcinoma under neoadjuvant chemotherapy: background-based adaptive-volume metrics outperform TLG and MTV in predicting histopathologic response. J Nucl Med. 2016;57:849–54.CrossRefGoogle Scholar
  7. 7.
    Dooms C, van Baardwijk A, Verbeken E, van Suylen RJ, Stroobants S, De Ruysscher D, et al. Association between 18F-fluoro-2-deoxy-d-glucose uptake values and tumor vitality: prognostic value of positron emission tomography in early-stage non-small cell lung cancer. J Thorac Oncol. 2009;4:822–8.CrossRefGoogle Scholar
  8. 8.
    Vesselle H, Salskov A, Turcotte E, Wiens L, Schmidt R, Jordan CD, et al. Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol. 2008;3:971–8.CrossRefGoogle Scholar
  9. 9.
    Semenza GL, editor. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Seminars in cancer biology. Amsterdam: Elsevier; 2009.Google Scholar
  10. 10.
    Shan X, Wang D, Chen J, Xiao X, Jiang Y, Wang Y, et al. Necrosis degree displayed in computed tomography images correlated with hypoxia and angiogenesis in breast cancer. J Comput Assist Tomogr. 2013;37:22–8.CrossRefGoogle Scholar
  11. 11.
    Schuurbiers OC, Meijer TW, Kaanders JH, Looijen-Salamon MG, de Geus-Oei LF, van der Drift MA, et al. Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma. J Thorac Oncol. 2014;9:1485–93.CrossRefGoogle Scholar
  12. 12.
    Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, et al. Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor. PLoS One. 2014;9:e86459.CrossRefGoogle Scholar
  13. 13.
    Fang YH, Lin CY, Shih MJ, Wang HM, Ho TY, Liao CT, et al. Development and evaluation of an open-source software package “CGITA” for quantifying tumor heterogeneity with molecular images. Biomed Res Int. 2014;2014:248505.Google Scholar
  14. 14.
    Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. The 2015 World Health Organization Classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10:1243–60.CrossRefGoogle Scholar
  15. 15.
    Jeong D, Ban S, Oh S, Jin Lee S, Yong Park S, Koh YW. Prognostic significance of EDIL3 expression and correlation with mesenchymal phenotype and microvessel density in lung adenocarcinoma. Sci Rep. 2017;7:8649.CrossRefGoogle Scholar
  16. 16.
    Pollheimer MJ, Kornprat P, Lindtner RA, Harbaum L, Schlemmer A, Rehak P, et al. Tumor necrosis is a new promising prognostic factor in colorectal cancer. Hum Pathol. 2010;41:1749–57.CrossRefGoogle Scholar
  17. 17.
    Larsen JE, Minna JD. Molecular biology of lung cancer: clinical implications. Clin Chest Med. 2011;32:703–40.CrossRefGoogle Scholar
  18. 18.
    Hirsch FR, Spreafico A, Novello S, Wood MD, Simms L, Papotti M. The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol. 2008;3:1468–81.CrossRefGoogle Scholar
  19. 19.
    Caruso R, Parisi A, Bonanno A, Paparo D, Quattrocchi E, Branca G, et al. Histologic coagulative tumour necrosis as a prognostic indicator of aggressiveness in renal, lung, thyroid and colorectal carcinomas: a brief review. Oncol Lett. 2012;3:16–8.CrossRefGoogle Scholar
  20. 20.
    Adams HJA, de Klerk JMH, Fijnheer R, Heggelman BGF, Dubois SV, Nievelstein RAJ, et al. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma. Eur J Radiol. 2016;85:304–9.CrossRefGoogle Scholar
  21. 21.
    Rakheja R, Makis W, Tulbah R, Skamene S, Holcroft C, Nahal A, et al. Necrosis on FDG PET/CT correlates with prognosis and mortality in sarcomas. AJR Am J Roentgenol. 2013;201:170–7.CrossRefGoogle Scholar
  22. 22.
    Foster JG, Wong SC, Sharp TV. The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol. 2014;10:2659–74.CrossRefGoogle Scholar
  23. 23.
    Daster S, Amatruda N, Calabrese D, Ivanek R, Turrini E, Droeser RA, et al. Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment. Oncotarget. 2017;8:1725–36.CrossRefGoogle Scholar
  24. 24.
    Chou CW, Wang CC, Wu CP, Lin YJ, Lee YC, Cheng YW, et al. Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1. Neuro Oncol. 2012;14:1227–38.CrossRefGoogle Scholar
  25. 25.
    Sasaki T, Yamamoto M, Yamaguchi T, Sugiyama S. Development of multicellular spheroids of HeLa cells cocultured with fibroblasts and their response to X-irradiation. Cancer Res. 1984;44:345–51.Google Scholar
  26. 26.
    Minakata K, Takahashi F, Nara T, Hashimoto M, Tajima K, Murakami A, et al. Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors. Cancer Sci. 2012;103:1946–54.CrossRefGoogle Scholar
  27. 27.
    Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond). 2012;7:597–615.CrossRefGoogle Scholar
  28. 28.
    Park SY, Cho A, Yu WS, Lee CY, Lee JG, Kim DJ, et al. Prognostic value of total lesion glycolysis by 18F-FDG PET/CT in surgically resected stage IA non-small cell lung cancer. J Nucl Med. 2015;56:45–9.CrossRefGoogle Scholar
  29. 29.
    Hyun SH, Ahn HK, Kim H, Ahn MJ, Park K, Ahn YC, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41:50–8.CrossRefGoogle Scholar
  30. 30.
    Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38.CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2018

Authors and Affiliations

  1. 1.Department of PathologyAjou University School of MedicineSuwonRepublic of Korea
  2. 2.Department of Nuclear Medicine and Molecular ImagingAjou University School of MedicineSuwon-siRepublic of Korea
  3. 3.Department of Thoracic and Cardiovascular SurgeryYonsei University College of MedicineSeoulRepublic of Korea

Personalised recommendations