Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 4/2016

01.04.2016 | Original Article

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

verfasst von: Edward E. Graves, Rodney J. Hicks, David Binns, Mathias Bressel, Quynh-Thu Le, Lester Peters, Richard J. Young, Danny Rischin

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
2.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
16.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat 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 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
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
25.
Zurück zum Zitat Carlin S, Humm JL. PET of hypoxia: current and future perspectives. J Nucl Med. 2012;53:1171–4.CrossRefPubMed Carlin S, Humm JL. PET of hypoxia: current and future perspectives. J Nucl Med. 2012;53:1171–4.CrossRefPubMed
Metadaten
Titel
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
verfasst von
Edward E. Graves
Rodney J. Hicks
David Binns
Mathias Bressel
Quynh-Thu Le
Lester Peters
Richard J. Young
Danny Rischin
Publikationsdatum
01.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 4/2016
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-015-3247-7

Weitere Artikel der Ausgabe 4/2016

European Journal of Nuclear Medicine and Molecular Imaging 4/2016 Zur Ausgabe

Society Communications

2015 Young Investigators Meeting