Skip to main content
Log in

Quantitative and qualitative analysis of [18F]FDG and [18F]FAZA positron emission tomography of head and neck cancers and associations with HPV status and treatment outcome

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

While methods for imaging tumor hypoxia with positron emission tomography (PET) have been developed, optimal methods for interpreting and utilizing these datasets in the clinic remain unclear. In this study, we analyzed hypoxia PET images of head and neck cancer patients and compared imaging metrics with human papilloma virus (HPV) status and clinical outcome.

Methods

Forty-one patients treated as part of a phase III trial of the hypoxic cytotoxin tirapazamine (TROG 02.02) were imaged with PET using fluorodeoxyglucose (FDG) and fluoroazomycin arabinoside (FAZA). FDG and FAZA PET images were interpreted qualitatively and quantitatively, and compared with tumor T stage, HPV status, and treatment outcome using multivariate statistics.

Results

PET signals in the tumor and lymph nodes exhibited significant intra- and inter-patient variability. The FAZA hypoxic volume demonstrated a significant correlation with tumor T stage. PET-hypoxic tumors treated with cisplatin exhibited significantly worse treatment outcomes relative to PET-oxic tumors or PET-hypoxic tumors treated with tirapazamine.

Conclusion

Quantitative analysis of FAZA PET yielded metrics that correlated with clinical T stage and were capable of stratifying patient outcome. These results encourage further development of this technology, with particular emphasis on establishment of robust quantitative methods.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OCA. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953;26:638–48.

    Article  CAS  PubMed  Google Scholar 

  2. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955;9:539–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Höckel M, Schlenger K, Knoop C, Vaupel P. Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Res. 1991;51:6098–102.

    PubMed  Google Scholar 

  4. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997;38:285–9.

    Article  CAS  PubMed  Google Scholar 

  5. Adam MF, Gabalski EC, Bloch DA, Oehlert JW, Brown JM, Elsaid AA, et al. Tissue oxygen distribution in head and neck cancer patients. Head Neck. 1999;21:146–53.

    Article  CAS  PubMed  Google Scholar 

  6. Nordsmark M, Bentzen SM, Rudat V, Brizel D, Lartigau E, Stadler P, et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol. 2005;77:18–24.

    Article  PubMed  Google Scholar 

  7. Rischin D, Hicks RJ, Fisher R, Binns D, Corry J, Porceddu S, et al. Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. J Clin Oncol. 2006;24:2098–104.

    Article  PubMed  Google Scholar 

  8. Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM. Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer. 2001;92:805–13.

    Article  CAS  PubMed  Google Scholar 

  9. Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28:4142–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Mortensen LS, Johansen J, Kallehauge J, Primdahl H, Busk M, Lassen P, et al. FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: results from the DAHANCA 24 trial. Radiother Oncol. 2012;105:14–20.

    Article  PubMed  Google Scholar 

  11. Rischin D, Peters LJ, O’Sullivan B, Giralt J, Fisher R, Yuen K, et al. Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group. J Clin Oncol. 2010;28:2989–95.

    Article  CAS  PubMed  Google Scholar 

  12. Peters LJ, O’Sullivan B, Giralt J, Fitzgerald TJ, Trotti A, Bernier J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02. J Clin Oncol. 2010;28:2996–3001.

    Article  PubMed  Google Scholar 

  13. Reischl G, Ehrlichmann W, Bieg C, Solbach C, Kumar P, Wiebe LI, et al. Preparation of the hypoxia imaging PET tracer [18F]FAZA: reaction parameters and automation. Appl Radiat Isot. 2005;62:897–901.

    Article  CAS  PubMed  Google Scholar 

  14. Graves EE, Quon A, Loo BW. RT_image: an open-source tool for investigating PET in radiation oncology. Technol Cancer Res Treat. 2007;6:111–21.

    Article  PubMed  Google Scholar 

  15. Thorwarth D, Eschmann SM, Holzner F, Paulsen F, Alber M. Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. Radiother Oncol. 2006;80:151–6.

    Article  CAS  PubMed  Google Scholar 

  16. La TH, Filion EJ, Turnbull BB, Chu JN, Lee P, Nguyen K, et al. Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2009;74:1335–41.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Rajendran JG, Schwartz DL, O’Sullivan J, Peterson LM, Ng P, Scharnhorst J, et al. Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res. 2006;12:5435–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Piert M, Machulla HJ, Picchio M, Rieschl G, Ziegler S, Kumar P, et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med. 2005;46:106–13.

    PubMed  Google Scholar 

  19. Beck R, Roper B, Carlsen J, Huisman M, Lebschi J, Andratschke N, et al. Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy using tirapazamine. J Nucl Med. 2007;48:973–80.

    Article  CAS  PubMed  Google Scholar 

  20. Souvatzoglou M, Grosu AL, Roper B, Krause BJ, Beck R, Reischl G, et al. Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study. Eur J Nucl Med Mol Imaging. 2007;34:1566–75.

    Article  CAS  PubMed  Google Scholar 

  21. Postema EJ, McEwan AJ, Riauka TA, Kumar P, Richmond DA, Abrams DN, et al. Initial results of hypoxia imaging using 1-alpha-D: −(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA). Eur J Nucl Med Mol Imaging. 2009;36:1565–73.

    Article  CAS  PubMed  Google Scholar 

  22. Rischin D, Fisher R, Peters L, Corry J, Hicks R. Hypoxia in head and neck cancer: studies with hypoxic positron emission tomography imaging and hypoxic cytotoxins. Int J Radiat Oncol Biol Phys. 2007;69:S61–3.

    Article  PubMed  Google Scholar 

  23. Goldenberg D, Begum S, Westra WH, Khan Z, Sciubba J, Pai SI, et al. Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck. 2008;30:898–903.

    Article  PubMed  Google Scholar 

  24. Trinkaus ME, Hicks RJ, Young RJ, Peters LJ, Solomon B, Bressel M, et al. Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer. J Med Imaging Radiat Oncol. 2014;58:89–97.

    Article  PubMed  Google Scholar 

  25. Carlin S, Humm JL. PET of hypoxia: current and future perspectives. J Nucl Med. 2012;53:1171–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was funded by the National Institutes of Health and the National Cancer Institute of the United States (R01 CA118582, P01 CA67166) and by the National Health and Medical Research Council of Australia.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Edward E. Graves.

Ethics declarations

Funding

This study was funded by the National Institutes of Health and the National Cancer Institute of the United States (R01 CA118582, P01 CA67166) and by the National Health and Medical Research Council of Australia.

Conflict of interest

E.E. Graves declares that he has no conflict of interest.

R.J. Hicks declares that he has no conflict of interest.

D. Binns declares that he has no conflict of interest.

M. Bressel declares that he has no conflict of interest.

Q.T. Le declares that she has no conflict of interest.

L. Peters declares that he has no conflict of interest.

R. Young declares that he has no conflict of interest.

D. Rischin declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Graves, E.E., Hicks, R.J., Binns, D. et al. Quantitative and qualitative analysis of [18F]FDG and [18F]FAZA positron emission tomography of head and neck cancers and associations with HPV status and treatment outcome. Eur J Nucl Med Mol Imaging 43, 617–625 (2016). https://doi.org/10.1007/s00259-015-3247-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-015-3247-7

Keywords

Navigation