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Potential of [18F]-Fluoromisonidazole positron-emission tomography for radiotherapy planning in head and neck squamous cell carcinomas

Möglichkeiten der [18F]-Fluormisonidazol-Positronenemissionstomographie für die Planung der Strahlentherapie bei Kopf-Hals-Tumoren

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Abstract

Background and purpose

Positron-emission tomography (PET) with [18F]-fluoromisonidazole (FMISO) permits consideration of radiotherapy dose escalation to hypoxic volumes in head and neck cancers (HNC). However, the definition of FMISO volumes remains problematic. The aims of this study are to confirm that delayed acquisition at 4 h is most appropriate for FMISO-PET imaging and to assess different methods of volume segmentation.

Patients and methods

A total of 15 HNC patients underwent several FMISO-PET/computed tomography (CT) acquisitions 2, 3 and 4 h after FMISO injection. Three automatic methods of PET image segmentation were tested: fixed threshold, adaptive threshold based on the ratio between tumour-derived and background activities (RT/B) and the fuzzy locally adaptive Bayesian (FLAB) method. The hypoxic fraction (HF), which is defined as the ratio between the FMISO and CT volumes, was also calculated.

Results

The RT/B for images acquired at 2, 3 and 4 h differed significantly, with mean values of 2.5 (1.7–2.9), 3 (2–4.5) and 3.4 (2.3–6.1), respectively. The mean tumour volume, as defined manually using CT images, was 39.1 ml (1.2–116 ml). After 4 h, the mean FMISO volumes were 18.9 (0.1–81), 9.5 (0.9–33.1) and 12.5 ml (0.9–38.4 ml) with fixed threshold, adaptive threshold and the FLAB method, respectively; median HF values were 0.47 (0.1–1.93), 0.25 (0.11–0.75) and 0.35 (0.14–1.05), respectively. FMISO volumes were significantly different.

Conclusion

The best contrast is obtained at the 4-hour acquisition time. Large discrepancies were found between the three tested methods of volume segmentation.

Zusammenfassung

Hintergrund und Ziel

Die Positronenemissionstomographie (PET) mit [18F]-Fluoromisonidazol (FMISO) ermöglicht in der Strahlentherapie für Kopf-Hals-Tumore (KHT) eine Dosissteigerung auf hypoxische Volumina. Allerdings bleibt die Bestimmung der FMISO-Volumina problematisch. Ziel dieser Studie ist es, verschiedene Volumen-Segmentierungsmethoden zu beurteilen und zu bestätigen, dass eine verzögerte Aufnahme von 4 h das Beste für die FMISO-PET-Bildgebung ist.

Patienten und Methoden

Insgesamt 15 KHT-Patienten unterzogen sich mehreren Aufnahmen einer FMISO-PET/Computertomographie (CT) jeweils 2, 3 und 4 h nach FMISO-Injektion. Es wurden drei automatische Segmentierungsmethoden von PET-Bildern getestet: ein fester Schwellenwert, ein adaptiver Schwellenwert, basierend auf dem Verhältnis zwischen den tumorösen und den Hintergrundaktivitäten (VT/H), sowie die „fuzzy-locally-adaptive-bayesian“-(FLAB-)Methode. Die hypoxische Fraktion (HF), die als das Verhältnis zwischen dem FMISO-Volumen und dem CT-Volumen definiert ist, wurde ebenfalls berechnet.

Ergebnisse

Die VT/H für Bilderaufnahmen nach 2, 3 und 4 h unterschieden sich mit einer mittleren Wert von jeweils 2,5 (1,7–2,9), 3 (2–4,5) und 3,4 (2,3–6,1) signifikant. Das mittlere, manuell mittels CT definierte Tumorvolumen betrug 39,1 ml (1,2–116). Nach 4 h ergaben sich mittlere FMISO-Volumina und eine mittlere HF von jeweils 18,9 ml (0,1–81) und 0,47 (0,1–1,93) mit dem festen Schwellenwert, 9,5 ml (0,9–33,1) und 0,25 (0,11–0,75) mit dem adaptiven Schwellenwert sowie 12,5 ml (0,9–38,4) und 0,35 (0,14–1,05) mit der FLAB-Methode. Die FMISO-Volumina waren signifikant unterschiedlich.

Schlussfolgerung

Den besten Kontrast erhält man bei der 4-Stunden-Aufnahme. Zwischen den drei getesteten Segmentierungsverfahren wurden große Unterschiede festgestellt.

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References

  1. Abolmaali N, Haase R, Koch A et al (2011) Two or four hour [18F]FMISO-PET in HNSCC. When is the contrast best? Nuklearmedizin 50(1):22–27

    Article  CAS  PubMed  Google Scholar 

  2. Bentzen SM, Gregoire V (2011) Molecular imaging-based dose painting: a novel paradigm for radiation therapy prescription. Semin Radiat Oncol 21(2):101–110

    Article  PubMed  Google Scholar 

  3. Dirix P, Vandecaveye V, Keyzer F De et al (2009) Dose painting in radiotherapy for head and neck squamous cell carcinoma: value of repeated functional imaging with (18)F-FDG PET, (18)F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI. J Nucl Med 50(7):1020–1027

    Article  PubMed  Google Scholar 

  4. Eschmann SM, Paulsen F, Bedeshem C et al (2007) Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. Radiother Oncol 83(3):406–410

    Article  CAS  PubMed  Google Scholar 

  5. Fodor A, Fiorino C, Dell’Oca I et al (2011) PET-guided dose escalation tomotherapy in malignant pleural mesothelioma. Strahlenther Onkol 187(11):736–743

    Article  PubMed  Google Scholar 

  6. Hatt M, Cheze le Rest C, Turzo A et al (2009) A fuzzy locally adaptive Bayesian segmentation approach for volume determination in PET. IEEE Trans Med Imaging 28(6):881–893

    Article  PubMed  Google Scholar 

  7. Hendrickson K, Phillips M, Smith W et al (2011) Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance. Radiother Oncol 101(3):369–375

    Article  PubMed  Google Scholar 

  8. Henriques de Figueiredo B, Barret O, Demeaux H et al (2009) Comparison between CT- and FDG-PET-defined target volumes for radiotherapy planning in head-and-neck cancers. Radiother Oncol 93(3):479–482

    Article  Google Scholar 

  9. Maftei C-A, Bayer C, Shi K, Vaupel P (2012) Intra- and intertumor heterogeneities in total, chronic, and acute hypoxia in xenografted squamous cell carcinomas. Detection and quantification using (immuno-)fluorescence techniques. Strahlenther Onkol 188(7):606–615

    Article  PubMed  Google Scholar 

  10. Le Maitre A, Hatt M, Pradier O et al (2012) Impact of the accuracy of automatic tumour functional volume delineation on radiotherapy treatment planning. Phys Med Biol 57(17):5381–5397

    Article  Google Scholar 

  11. Nehmeh SA, Lee NY, Schröder H et al (2008) Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. Int J Radiat Oncol Biol Phys 70(1):235–242

    Article  CAS  PubMed  Google Scholar 

  12. Nordsmark M, Bentzen SM, Rudat V et al (2005) Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 77(1):18–24

    Article  PubMed  Google Scholar 

  13. Okamoto S, Shiga T, Yasuda K et al (2013) High reproducibility of tumor hypoxia evaluated by 18F-Fluoromisonidazole PET for head and neck cancer. J Nucl Med 54(2):201–207

    Article  CAS  PubMed  Google Scholar 

  14. Overgaard J, Horsman MR (1996) Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol 6(1):10–21

    Article  PubMed  Google Scholar 

  15. Pinkawa M, Holy R, Piroth MD et al (2010) Intensity-modulated radiotherapy for prostate cancer implementing molecular imaging with 18F-choline PET-CT to define a simultaneous integrated boost. Strahlenther Onkol 186(11):600–606

    Article  PubMed  Google Scholar 

  16. Popple RA, Ove R, Shen S (2002) Tumor control probability for selective boosting of hypoxic subvolumes, including the effect of reoxygenation. Int J Radiat Oncol Biol Phys 54(3):921–927

    Article  PubMed  Google Scholar 

  17. Rajendran JG, Schwartz DL, O’Sullivan J et al (2006) Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res 12(18):5435–5441

    Article  CAS  PubMed  Google Scholar 

  18. Thorwarth D, Eschmann S-M, Paulsen F, Alber M (2007) Hypoxia dose painting by numbers: a planning study. Int J Radiat Oncol Biol Phys 68(1):291–300

    Article  PubMed  Google Scholar 

  19. Zips D, Zöphel K, Abolmaali N et al (2012) Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. Radiother Oncol 105(1):21–28

    Article  PubMed  Google Scholar 

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Funding

No funding was received for this study.

Acknowledgements

The authors thank Pippa McKelvie-Sebileau for medical editorial assistance in English.

Compliance with ethical guidelines

Conflict of interest. B. Henriques de Figueiredo, T. Merlin, H. de Clermont-Gallerande, M. Hatt, D. Vimont, P. Fernandez and F. Lamare state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Correspondence to B. Henriques de Figueiredo M.D..

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Henriques de Figueiredo, B., Merlin, T., de Clermont-Gallerande, H. et al. Potential of [18F]-Fluoromisonidazole positron-emission tomography for radiotherapy planning in head and neck squamous cell carcinomas. Strahlenther Onkol 189, 1015–1019 (2013). https://doi.org/10.1007/s00066-013-0454-7

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