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Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour’s biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [18F]FDG, a new hypoxia tracer [18F]EF5 and the perfusion tracer [15O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.

Methods

The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [15O]H2O PET images using a one-tissue compartment model. [18F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [18F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival.

Results

Tumour stage and T-classification did not show any significant differences in comparison to the patients’ metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [18F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [18F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [18F]FDG SUVmax, [18F]EF5 T/M ratio and blood flow.

Conclusion

Our study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [18F]EF5 showed a stronger correlation with a poor clinical outcome than [18F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [18F]EF5 may act as a surrogate marker of radioresistance.

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References

  1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.

    Article  PubMed  CAS  Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  3. Troost EG, Schinagl DA, Bussink J, Oyen WJ, Kaanders JH. Clinical evidence on PET-CT for radiation therapy planning in head and neck tumours. Radiother Oncol. 2010;96:328–34.

    Article  PubMed  Google Scholar 

  4. Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol. 1996;41:31–9.

    Article  PubMed  CAS  Google Scholar 

  5. Vesselle H, Freeman JD, Wiens L, Stern J, Nguyen HQ, Hawes SE, et al. Fluorodeoxyglucose uptake of primary non-small cell lung cancer at positron emission tomography: new contrary data on prognostic role. Clin Cancer Res. 2007;13:3255–63.

    Article  PubMed  CAS  Google Scholar 

  6. Ang KK. More lessons learned from the suffocation of hypoxia. J Clin Oncol. 2010;28:2941–3.

    Article  PubMed  Google Scholar 

  7. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Komar G, Seppanen M, Eskola O, Lindholm P, Gronroos TJ, Forsback S, et al. 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med. 2008;49:1944–51.

    Article  PubMed  Google Scholar 

  9. Eskola O, Grönroos TJ, Forsback S, Tuomela J, Komar G, Bergman J, et al. Tracer level electrophilic synthesis and pharmacokinetics of the hypoxia tracer [(18)F]EF5. Mol Imaging Biol. 2012;14:205–12.

    Article  PubMed  Google Scholar 

  10. Teras M, Tolvanen T, Johansson JJ, Williams JJ, Knuuti J. Performance of the new generation of whole-body PET/CT scanners: Discovery STE and Discovery VCT. Eur J Nucl Med Mol Imaging. 2007;34:1683–92.

    Article  PubMed  CAS  Google Scholar 

  11. Blomqvist G. On the construction of functional maps in positron emission tomography. J Cereb Blood Flow Metab. 1984;4:629–32.

    Article  PubMed  CAS  Google Scholar 

  12. Lawson CL, Hanson RJ. Solving least squares problems. Philadelphia, PA: Society for Industrial Mathematics; 1987

    Google Scholar 

  13. Meyer E. Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET. J Nucl Med. 1989;30:1069–78.

    PubMed  CAS  Google Scholar 

  14. Van den Hoff J, Burchert W, Muller-Schauenburg W, Meyer GJ, Hundeshagen H. Accurate local blood flow measurements with dynamic PET: fast determination of input function delay and dispersion by multilinear minimization. J Nucl Med. 1993;34:1770–7.

    PubMed  Google Scholar 

  15. Komar G, Oikonen V, Sipilä H, Seppänen M, Minn H. Noninvasive parametric blood flow imaging of head and neck tumours using [15O]H2O and PET/CT. Nucl Med Commun. 2012;33:1169–78.

    Article  PubMed  Google Scholar 

  16. Haerle SK, Huber GF, Hany TF, Ahmad N, Schmid DT. Is there a correlation between 18F-FDG-PET standardized uptake value, T-classification, histological grading and the anatomic subsites in newly diagnosed squamous cell carcinoma of the head and neck? Eur Arch Otorhinolaryngol. 2010;267:1635–40.

    Article  PubMed  Google Scholar 

  17. 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 

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

    Article  PubMed  CAS  Google Scholar 

  19. Clavo AC, Brown RS, Wahl RL. Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. J Nucl Med. 1995;36:1625–32.

    PubMed  CAS  Google Scholar 

  20. Minn H, Clavo AC, Wahl RL. Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. Nucl Med Biol. 1996;23:941–6.

    Article  PubMed  CAS  Google Scholar 

  21. Busk M, Horsman MR, Jakobsen S, Bussink J, van der Kogel A, Overgaard J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging. 2008;35:2294–303.

    Article  PubMed  CAS  Google Scholar 

  22. Suzuki H, Kato K, Fujimoto Y, Itoh Y, Hiramatsu M, Maruo T, et al. (18)F-FDG-PET/CT predicts survival in hypopharyngeal squamous cell carcinoma. Ann Nucl Med. 2013;27:297–302.

    Article  PubMed  CAS  Google Scholar 

  23. Schinagl DA, Span PN, Oyen WJ, Kaanders JH. Can FDG PET predict radiation treatment outcome in head and neck cancer? Results of a prospective study. Eur J Nucl Med Mol Imaging. 2010;38:1449–58.

    Article  Google Scholar 

  24. Romesser PB, Qureshi MM, Shah BA, Chatburn LT, Jalisi S, Devaiah AK, et al. Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy. Ann Nucl Med. 2012;26:527–34.

    Article  PubMed  Google Scholar 

  25. Hatt M, Visvikis D, Albarghach NM, Tixier F, Pradier O, Cheze-le Rest C. Prognostic value of 18F-FDG PET image-based parameters in oesophageal cancer and impact of tumour delineation methodology. Eur J Nucl Med Mol Imaging. 2011;38:1191–202

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the staff at the Turku PET Centre, the Department of Oncology and Radiotherapy, and the Department of Otorhinolaryngology for help in various phases of this project. We would also like to thank Irina Lisinen, MSC, for her help with the statistical analysis. The study was financially supported by the European Union’s FP6 Commission BioCare (Molecular Imaging for Biologically Optimized Cancer Therapy), under contract number 505785, by the Finnish Cancer Organizations and by the Turku University Foundation.

Conflicts of interest

None.

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Authors and Affiliations

  1. Turku PET Centre, Kiinamyllynkatu 4-8, 20521, Turku, Finland

    Gaber Komar, Marko Seppänen, Olli Eskola, Hannu Sipilä, Olof Solin & Heikki Minn

  2. Department of Oncology and Radiotherapy, Turku University Hospital and University of Turku, Turku, Finland

    Kaisa Lehtiö, Helena Levola, Paula Lindholm, Jan Seppälä & Heikki Minn

  3. Department of Nuclear Medicine, Turku University Hospital and University of Turku, Turku, Finland

    Marko Seppänen

  4. Department of Otorhinolaryngology, Head and Neck Surgery, Turku University Hospital and University of Turku, Turku, Finland

    Reidar Grénman

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  1. Gaber Komar
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Correspondence to Gaber Komar.

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Komar, G., Lehtiö, K., Seppänen, M. et al. Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy. Eur J Nucl Med Mol Imaging 41, 2042–2050 (2014). https://doi.org/10.1007/s00259-014-2818-3

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  • DOI: https://doi.org/10.1007/s00259-014-2818-3

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