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Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2005

01-12-2005 | Original Article

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

Authors: Rodney J. Hicks, Danny Rischin, Richard Fisher, David Binns, Andrew M. Scott, Lester J. Peters

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2005

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Abstract

Purpose

The purpose of the study was to evaluate [18F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy.

Methods

Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [18F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort.

Results

Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27–73%), the 5-year failure-free survival was 44% (95% CI 22–68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38–88%).

Conclusion

The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.
Literature
1.
go back to reference Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 2000;355:949–55PubMed Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 2000;355:949–55PubMed
2.
go back to reference Gray LH, Conger AD, Ebert M, Hornesy S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953;26:638–48PubMed Gray LH, Conger AD, Ebert M, Hornesy S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953;26:638–48PubMed
3.
go back to reference Gatenby RA, Kessler HB, Rosenblum JS, Coia LR, Moldofsky PJ, Hartz WH, et al. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1988;14:831–8PubMed Gatenby RA, Kessler HB, Rosenblum JS, Coia LR, Moldofsky PJ, Hartz WH, et al. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1988;14:831–8PubMed
4.
go back to reference Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 1996;41:31–9PubMed Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 1996;41:31–9PubMed
5.
go back to reference Nordsmark M, Overgaard J. A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 2000;57:39–43CrossRefPubMed Nordsmark M, Overgaard J. A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 2000;57:39–43CrossRefPubMed
6.
go back to reference 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;38:285–9CrossRefPubMed 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;38:285–9CrossRefPubMed
7.
go back to reference Brown JM. SR 4233 (tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours. Br J Cancer 1993;67:1163–70PubMed Brown JM. SR 4233 (tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours. Br J Cancer 1993;67:1163–70PubMed
8.
go back to reference Rischin D, Peters L, Hicks R, Hughes P, Fisher R, Hart R, et al. Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. J Clin Oncol 2001;19:535–42PubMed Rischin D, Peters L, Hicks R, Hughes P, Fisher R, Hart R, et al. Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. J Clin Oncol 2001;19:535–42PubMed
9.
go back to reference Brown JM, Lemmon MJ. Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors. Cancer Res 1990;50:7745–9PubMed Brown JM, Lemmon MJ. Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors. Cancer Res 1990;50:7745–9PubMed
10.
go back to reference Dorie MJ, Brown JM. Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin. Cancer Res 1993;53:4633–6PubMed Dorie MJ, Brown JM. Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin. Cancer Res 1993;53:4633–6PubMed
11.
go back to reference Benard F, Smith RJ, Hustinx R, Karp JS, Alavi A. Clinical evaluation of processing techniques for attenuation correction with 137Cs in whole-body PET imaging. J Nucl Med 1999;40:1257–63PubMed Benard F, Smith RJ, Hustinx R, Karp JS, Alavi A. Clinical evaluation of processing techniques for attenuation correction with 137Cs in whole-body PET imaging. J Nucl Med 1999;40:1257–63PubMed
12.
go back to reference Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys. 2000;47(3):551–60CrossRefPubMed Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys. 2000;47(3):551–60CrossRefPubMed
13.
go back to reference MacManus MP, Hicks RJ, Matthews JP, Hogg A, McKenzie AF, Wirth A, et al. High rate of detection of unsuspected distant metastases by PET in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. Int J Radiat Oncol Biol Phys 2001;50:287–93CrossRefPubMed MacManus MP, Hicks RJ, Matthews JP, Hogg A, McKenzie AF, Wirth A, et al. High rate of detection of unsuspected distant metastases by PET in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. Int J Radiat Oncol Biol Phys 2001;50:287–93CrossRefPubMed
14.
go back to reference Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003;3:347–61 Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003;3:347–61
15.
go back to reference Rasey JS, Martin GV, Krohn KA. Quantifying hypoxia with radiolabeled fluoromisonidazole: pre-clinical and clinical studies. In: Machulla H-J, editor. Imaging of hypoxia. Dordrecht: Kluwer Academic Publishers; 1999. p. 85–117 Rasey JS, Martin GV, Krohn KA. Quantifying hypoxia with radiolabeled fluoromisonidazole: pre-clinical and clinical studies. In: Machulla H-J, editor. Imaging of hypoxia. Dordrecht: Kluwer Academic Publishers; 1999. p. 85–117
16.
go back to reference Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, et al. Prognostic Impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005;46:253–60PubMed Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, et al. Prognostic Impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005;46:253–60PubMed
17.
go back to reference Evans SM, Koch CJ. Prognostic significance of tumor oxygenation in humans. Cancer Lett 2003;195:1–16CrossRefPubMed Evans SM, Koch CJ. Prognostic significance of tumor oxygenation in humans. Cancer Lett 2003;195:1–16CrossRefPubMed
18.
go back to reference Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 1996;36:417–28CrossRefPubMed Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 1996;36:417–28CrossRefPubMed
19.
go back to reference Hicks R, Rischin D, Fisher R, Binns D, Corry J, Porceddu S, et al. Superiority of tirapazamine-containing chemoradiation in head and neck cancers showing evidence of hypoxia on 18F-misonidazole (FMISO) PET scanning. Proc Am Soc Clin Oncol 2004;23:491 Hicks R, Rischin D, Fisher R, Binns D, Corry J, Porceddu S, et al. Superiority of tirapazamine-containing chemoradiation in head and neck cancers showing evidence of hypoxia on 18F-misonidazole (FMISO) PET scanning. Proc Am Soc Clin Oncol 2004;23:491
20.
go back to reference Eschmann S-R, Paulsen F, Reimold M, Dittman H, Welz S, Reischl G, et al. Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005;46:253–60PubMed Eschmann S-R, Paulsen F, Reimold M, Dittman H, Welz S, Reischl G, et al. Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005;46:253–60PubMed
Metadata
Title
Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent
Authors
Rodney J. Hicks
Danny Rischin
Richard Fisher
David Binns
Andrew M. Scott
Lester J. Peters
Publication date
01-12-2005
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2005
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-005-1880-2

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