Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Effect of radiochemotherapy on T2* MRI in HNSCC and its relation to FMISO PET derived hypoxia and FDG PET

Authors: Nicole Wiedenmann, Hatice Bunea, Hans C. Rischke, Andrei Bunea, Liette Majerus, Lars Bielak, Alexey Protopopov, Ute Ludwig, Martin Büchert, Christian Stoykow, Nils H. Nicolay, Wolfgang A. Weber, Michael Mix, Philipp T. Meyer, Jürgen Hennig, Michael Bock, Anca L. Grosu

Published in: Radiation Oncology | Issue 1/2018

Login to get access

Abstract

Background

To assess the effect of radiochemotherapy (RCT) on proposed tumour hypoxia marker transverse relaxation time (T2*) and to analyse the relation between T2* and 18F-misonidazole PET/CT (FMISO-PET) and 18F-fluorodeoxyglucose PET/CT (FDG-PET).

Methods

Ten patients undergoing definitive RCT for squamous cell head-and-neck cancer (HNSCC) received repeat FMISO- and 3 Tesla T2*-weighted MRI at weeks 0, 2 and 5 during treatment and FDG-PET at baseline. Gross tumour volumes (GTV) of tumour (T), lymph nodes (LN) and hypoxic subvolumes (HSV, based on FMISO-PET) and complementary non-hypoxic subvolumes (nonHSV) were generated. Mean values for T2* and SUVmean FDG were determined.

Results

During RCT, marked reduction of tumour hypoxia on FMISO-PET was observed (T, LN), while mean T2* did not change significantly. At baseline, mean T2* values within HSV-T (15 ± 5 ms) were smaller compared to nonHSV-T (18 ± 3 ms; p = 0.051), whereas FDG SUVmean (12 ± 6) was significantly higher for HSV-T (12 ± 6) than for nonHSV-T (6 ± 3; p = 0.026) and higher for HSV-LN (10 ± 4) than for nonHSV-LN (5 ± 2; p ≤ 0.011). Correlation between FMISO PET and FDG PET was higher than between FMSIO PET and T2* (R2 for GTV-T (FMISO/FDG) = 0.81, R2 for GTV-T (FMISO/T2*) = 0.32).

Conclusions

Marked reduction of tumour hypoxia between week 0, 2 and 5 found on FMISO PET was not accompanied by a significant T2*change within GTVs over time. These results suggest a relation between tumour oxygenation status and T2* at baseline, but no simple correlation over time. Therefore, caution is warranted when using T2* as a substitute for FMISO-PET to monitor tumour hypoxia during RCT in HNSCC patients.

Trial registration

DRKS, DRKS00003830 . Registered 23.04.2012.

Literature
  1. Thorwarth D, Eschmann SM, Scheiderbauer J, Paulsen F, Alber M. Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer. 2005;5:152.View ArticlePubMedPubMed Central
  2. 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.View ArticlePubMedPubMed Central
  3. Padhani AR, Krohn KA, Lewis JS, Alber M. Imaging oxygenation of human tumours. Eur Radiol. 2007;17:861–72.View ArticlePubMed
  4. Zips D, Zophel K, Abolmaali N, Perrin R, Abramyuk A, Haase R, et al. Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. Radiother Oncol. 2012;105:21–8.View ArticlePubMed
  5. Alber M, Thorwarth D. Multi-modality functional image guided dose escalation in the presence of uncertainties. Radiother Oncol. 2014;111:354–9.View ArticlePubMed
  6. Schutze C, Bergmann R, Bruchner K, Mosch B, Yaromina A, Zips D, et al. Effect of [(18)F]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice. Radiother Oncol. 2014;111:81–7.View ArticlePubMed
  7. Wiedenmann NE, Bucher S, Hentschel M, Mix M, Vach W, Bittner MI, et al. Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome. Radiother Oncol. 2015;117:113–7.
  8. Bittner MI, Wiedenmann N, Bucher S, Hentschel M, Mix M, Weber WA, et al. Exploratory geographical analysis of hypoxic subvolumes using 18F-MISO-PET imaging in patients with head and neck cancer in the course of primary chemoradiotherapy. Radiotherapy Oncol. 2013;108:511–6.View Article
  9. Thorwarth D. Biologically adapted radiation therapy. Z Med Phys. 2018;28(3):177–83.
  10. Welz S, Monnich D, Pfannenberg C, Nikolaou K, Reimold M, La Fougere C, et al. Prognostic value of dynamic hypoxia PET in head and neck cancer: results from a planned interim analysis of a randomized phase II hypoxia-image guided dose escalation trial. RadiotherOncol. 2017;124:526–32.
  11. Boeke S, Thorwarth D, Monnich D, Pfannenberg C, Reischl G, La Fougere C, et al. Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer. Acta oncologica (Stockholm, Sweden). 2017;56:1571–6.View Article
  12. Lock S, Perrin R, Seidlitz A, Bandurska-Luque A, Zschaeck S, Zophel K, et al. Residual tumour hypoxia in head-and-neck cancer patients undergoing primary radiochemotherapy, final results of a prospective trial on repeat FMISO-PET imaging. Radiother Oncol. 2017;124:533–40.View ArticlePubMed
  13. Grkovski M, Schoder H, Lee NY, Carlin SD, Beattie BJ, Riaz N, et al. Multiparametric imaging of tumor hypoxia and perfusion with 18F-Fluoromisonidazole dynamic PET in head and neck Cancer. J Nucl Med. 2017;58:1072–80.View ArticlePubMedPubMed Central
  14. Linge A, Lohaus F, Lock S, Nowak A, Gudziol V, Valentini C, et al. HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: a multicentre retrospective study of the German Cancer consortium radiation oncology group (DKTK-ROG). Radiother Oncol. 2016;121:364–73.View ArticlePubMed
  15. Peeters SG, Zegers CM, Lieuwes NG, van Elmpt W, Eriksson J, van Dongen GA, et al. A comparative study of the hypoxia PET tracers [(1)(8)F]HX4, [(1)(8)F]FAZA, and [(1)(8)F]FMISO in a preclinical tumor model. Int J Radiat Oncol Biol Phys. 2015;91:351–9.View ArticlePubMed
  16. Carlin S, Zhang H, Reese M, Ramos NN, Chen Q, Ricketts SA. A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers. J Nucl Med. 2014;55:515–21.View ArticlePubMed
  17. Wack LJ, Monnich D, van Elmpt W, Zegers CM, Troost EG, Zips D, et al. Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia--a simulation study. Acta oncologica (Stockholm, Sweden). 2015;54:1370–7.View Article
  18. Grosu AL, Souvatzoglou M, Roper B, Dobritz M, Wiedenmann N, Jacob V, et al. Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;69:541–51.View ArticlePubMed
  19. Baudelet C, Ansiaux R, Jordan BF, Havaux X, Macq B, Gallez B. Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia? Phys Med Biol. 2004;49:3389–411.View ArticlePubMed
  20. Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics. 2009;29:1433–49.View ArticlePubMedPubMed Central
  21. Christen T, Lemasson B, Pannetier N, Farion R, Remy C, Zaharchuk G, et al. Is T2* enough to assess oxygenation? Quantitative blood oxygen level-dependent analysis in brain tumor. Radiology. 2012;262:495–502.View ArticlePubMedPubMed Central
  22. Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990;87:9868–72.View ArticlePubMedPubMed Central
  23. Panek R, Welsh L, Dunlop A, Wong KH, Riddell AM, Koh DM, et al. Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T. J Magn Reson Imaging. 2016;44:72–80.View ArticlePubMedPubMed Central
  24. Prielmeier F, Nagatomo Y, Frahm J. Cerebral blood oxygenation in rat brain during hypoxic hypoxia. Quantitative MRI of effective transverse relaxation rates. Magn Reson Med. 1994;31:678–81.View ArticlePubMed
  25. Punwani S, Ordidge RJ, Cooper CE, Amess P, Clemence M. MRI measurements of cerebral deoxyhaemoglobin concentration [dHb]--correlation with near infrared spectroscopy (NIRS). NMR Biomed. 1998;11:281–9.View ArticlePubMed
  26. Taylor NJ, Baddeley H, Goodchild KA, Powell ME, Thoumine M, Culver LA, et al. BOLD MRI of human tumor oxygenation during carbogen breathing. J Magn Reson Imaging. 2001;14:156–63.View ArticlePubMed
  27. Hallac RR, Ding Y, Yuan Q, McColl RW, Lea J, Sims RD, et al. Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level-dependent (BOLD) MRI at 3T. NMR Biomed. 2012;25:1321–30.View ArticlePubMedPubMed Central
  28. Zhou H, Zhang Z, Denney R, Williams JS, Gerberich J, Stojadinovic S, et al. Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging. Oncotarget. 2017;8:37464–77.PubMedPubMed Central
  29. Kim CK, Park SY, Park BK, Park W, Huh SJ. Blood oxygenation level-dependent MR imaging as a predictor of therapeutic response to concurrent chemoradiotherapy in cervical cancer: a preliminary experience. Eur Radiol. 2014;24:1514–20.View ArticlePubMed
  30. Li XS, Fan HX, Fang H, Song YL, Zhou CW. Value of R2* obtained from T2*-weighted imaging in predicting the prognosis of advanced cervical squamous carcinoma treated with concurrent chemoradiotherapy. J Magn Reson Imaging. 2015;42:681–8.View ArticlePubMed
  31. Wacker CM, Bock M, Hartlep AW, Beck G, van Kaick G, Ertl G, et al. Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole: assessment using T*2 and T1 measurements. Magn Reson Med. 1999;41:686–95.View ArticlePubMed
  32. Preibisch C, Shi K, Kluge A, Lukas M, Wiestler B, Göttler J, et al. Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study. NMR Biomed. 2017;30(11). https://​doi.​org/​10.​1002/​nbm.​3775
  33. Min M, Lee MT, Lin P, Holloway L, Wijesekera D, Gooneratne D, et al. Assessment of serial multi-parametric functional MRI (diffusion-weighted imaging and R2*) with (18)F-FDG-PET in patients with head and neck cancer treated with radiation therapy. Br J Radiol. 2016;89:20150530.View ArticlePubMedPubMed Central
  34. Wong KH, Panek R, Dunlop A, Mcquaid D, Riddell A, Welsh LC, et al. Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer. Eur J Nucl Med Mol Imaging. 2018;45(5):759–67.
  35. Thorwarth D, Monnich D, Zips D. Methodological aspects on hypoxia PET acquisition and image processing. Q J Nucl Med Mol Imaging. 2013;57:235–43.PubMed
  36. Bittner MI, Wiedenmann N, Bucher S, Hentschel M, Mix M, Rucker G, et al. Analysis of relation between hypoxia PET imaging and tissue-based biomarkers during head and neck radiochemotherapy. Acta oncologica (Stockholm, Sweden). 2016;55:1299–304.View Article
  37. Leibfarth S, Simoncic U, Monnich D, Welz S, Schmidt H, Schwenzer N, et al. Analysis of pairwise correlations in multi-parametric PET/MR data for biological tumor characterization and treatment individualization strategies. Eur J Nucl Med Mol Imaging. 2016;43:1199–208.View ArticlePubMedPubMed Central
  38. Simoncic U, Leibfarth S, Welz S, Schwenzer N, Schmidt H, Reischl G, et al. Comparison of DCE-MRI kinetic parameters and FMISO-PET uptake parameters in head and neck cancer patients. Med Phys. 2017;44:2358–68.View ArticlePubMed
  39. Monnich D, Thorwarth D, Leibfarth S, Pfannenberg C, Reischl G, Mauz PS, et al. Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer. Acta oncologica (Stockholm, Sweden). 2017;56:1577–82.View Article
  40. Wedegartner U, Kooijman H, Andreas T, Beindorff N, Hecher K, Adam G. T2 and T2* measurements of fetal brain oxygenation during hypoxia with MRI at 3T: correlation with fetal arterial blood oxygen saturation. Eur Radiol. 2010;20:121–7.View ArticlePubMed
  41. Panek R, Welsh L, Baker LCJ, Schmidt MA, Wong KH, Riddell AM, et al. Noninvasive imaging of cycling hypoxia in head and neck Cancer using intrinsic susceptibility MRI. Clin Cancer Res. 2017;23:4233–41.View ArticlePubMedPubMed Central
  42. Welsh L, Panek R, Riddell A, Wong K, Leach MO, Tavassoli M, et al. Blood transfusion during radical chemo-radiotherapy does not reduce tumour hypoxia in squamous cell cancer of the head and neck. Br J Cancer. 2017;116:28–35.View ArticlePubMed
  43. Hallac RR, Zhou H, Pidikiti R, Song K, Stojadinovic S, Zhao D, et al. Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response. Magn Reson Med. 2014;71:1863–73.View ArticlePubMed
  44. Mainta IC, Zilli T, Tille JC, De Perrot T, Vallée JP, Buchegger F, Garibotto V, Miralbell R. The effect of neoadjuvant androgen deprivation therapy on tumor hypoxia in high-grade prostate cancer: an (18)F-MISO PET-MRI study. Int J Radiat Oncol Biol Phys. 2018. https://​doi.​org/​10.​1016/​j.​ijrobp.​2018.​02.​170.
Metadata
Title
Effect of radiochemotherapy on T2* MRI in HNSCC and its relation to FMISO PET derived hypoxia and FDG PET
Authors
Nicole Wiedenmann
Hatice Bunea
Hans C. Rischke
Andrei Bunea
Liette Majerus
Lars Bielak
Alexey Protopopov
Ute Ludwig
Martin Büchert
Christian Stoykow
Nils H. Nicolay
Wolfgang A. Weber
Michael Mix
Philipp T. Meyer
Jürgen Hennig
Michael Bock
Anca L. Grosu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-1103-1

Other articles of this Issue 1/2018

Radiation Oncology 1/2018 Go to the issue

Research

Improve dosimetric outcome in stage III non-small-cell lung cancer treatment using spot-scanning proton arc (SPArc) therapy

Research

Light and shadows of a new technique: is photon total-skin irradiation using helical IMRT feasible, less complex and as toxic as the electrons one?

Research

Prognostic factors of radiation dermatitis following passive-scattering proton therapy for breast cancer

Research

Worth a local treatment? – Analysis of modern radiotherapy concepts for oligometastatic prostate cancer

Research

Image-guided radiotherapy reduces the risk of under-dosing high-risk prostate cancer extra-capsular disease and improves biochemical control

Research

The potential failure risk of the cone-beam computed tomography-based planning target volume margin definition for prostate image-guided radiotherapy based on a prospective single-institutional hybrid analysis