Dose Escalation Using Hypoxia-adjusted Radiotherapy

Summary

DE-HyART is a phase II clinical trial aimed at understanding the effects of escalating radiation doses to hypoxic sub-volumes inherent to squamous cell head and neck cancer. The study is aimed at assessing locoregional control, feasibility, and acceptable toxicity with such a strategy.

Timeline

Start

2024-04-08

Primary completion

2028-04

Completion

2028-04

Publications

• Background Mortensen LS, Johansen J, Kallehauge J, Primdahl H, Busk M, Lassen P, Alsner J, Sorensen BS, Toustrup K, Jakobsen S, Petersen J, Petersen H, Theil J, Nordsmark M, Overgaard J. 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 Oct;105(1):14-20. doi: 10.1016/j.radonc.2012.09.015. Epub 2012 Oct 16.
• Background Lock S, Perrin R, Seidlitz A, Bandurska-Luque A, Zschaeck S, Zophel K, Krause M, Steinbach J, Kotzerke J, Zips D, Troost EGC, Baumann M. 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 Sep;124(3):533-540. doi: 10.1016/j.radonc.2017.08.010. Epub 2017 Aug 23.
• Background Kikuchi M, Yamane T, Shinohara S, Fujiwara K, Hori SY, Tona Y, Yamazaki H, Naito Y, Senda M. 18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma. Ann Nucl Med. 2011 Nov;25(9):625-33. doi: 10.1007/s12149-011-0508-9. Epub 2011 Jul 1.
• Background 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(2 Suppl):S61-3. doi: 10.1016/j.ijrobp.2007.05.043. No abstract available.
• Background Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol. 1996 Oct;41(1):31-9. doi: 10.1016/s0167-8140(96)91811-3.
• Background Tandon S, Gairola M, Ahlawat P, Karimi AM, Tiwari S, Muttagi V, Sachdeva N, Sharief MI, Dobriyal K. Failure patterns of head and neck squamous cell carcinoma treated with radical radiotherapy by intensity modulated radiotherapy technique using focal volume and dosimetric method. Head Neck. 2019 Jun;41(6):1632-1637. doi: 10.1002/hed.25586. Epub 2018 Dec 23.
• Background Bourhis J, Le Maitre A, Baujat B, Audry H, Pignon JP; Meta-Analysis of Chemotherapy in Head, Neck Cancer Collaborative Group; Meta-Analysis of Radiotherapy in Carcinoma of Head, Neck Collaborative Group; Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma Collaborative Group. Individual patients' data meta-analyses in head and neck cancer. Curr Opin Oncol. 2007 May;19(3):188-94. doi: 10.1097/CCO.0b013e3280f01010.
• Background Brockstein B, Haraf DJ, Rademaker AW, Kies MS, Stenson KM, Rosen F, Mittal BB, Pelzer H, Fung BB, Witt ME, Wenig B, Portugal L, Weichselbaum RW, Vokes EE. Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience. Ann Oncol. 2004 Aug;15(8):1179-86. doi: 10.1093/annonc/mdh308.
• Background Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. doi: 10.1056/NEJMoa070956.
• Background Pignon JP, le Maitre A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 14.
• Background Zegers CM, Hoebers FJ, van Elmpt W, Bons JA, Ollers MC, Troost EG, Eekers D, Balmaekers L, Arts-Pechtold M, Mottaghy FM, Lambin P. Evaluation of tumour hypoxia during radiotherapy using [18F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2139-2146. doi: 10.1007/s00259-016-3429-y. Epub 2016 Jun 1.
• Background Zschaeck S, Lock S, Hofheinz F, Zips D, Sakso Mortensen L, Zophel K, Troost EGC, Boeke S, Sakso M, Monnich D, Seidlitz A, Johansen J, Skripcak T, Gregoire V, Overgaard J, Baumann M, Krause M. Individual patient data meta-analysis of FMISO and FAZA hypoxia PET scans from head and neck cancer patients undergoing definitive radio-chemotherapy. Radiother Oncol. 2020 Aug;149:189-196. doi: 10.1016/j.radonc.2020.05.022. Epub 2020 May 15.
• Results Welz S, Paulsen F, Pfannenberg C, Reimold M, Reischl G, Nikolaou K, La Fougere C, Alber M, Belka C, Zips D, Thorwarth D. Dose escalation to hypoxic subvolumes in head and neck cancer: A randomized phase II study using dynamic [18F]FMISO PET/CT. Radiother Oncol. 2022 Jun;171:30-36. doi: 10.1016/j.radonc.2022.03.021. Epub 2022 Apr 5.
• Results Pigorsch SU, Wilkens JJ, Kampfer S, Kehl V, Hapfelmeier A, Schlager C, Bier H, Schwaiger M, Combs SE. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol. Radiat Oncol. 2017 Mar 1;12(1):45. doi: 10.1186/s13014-017-0776-1.
• Results Rajendran JG, Hendrickson KR, Spence AM, Muzi M, Krohn KA, Mankoff DA. Hypoxia imaging-directed radiation treatment planning. Eur J Nucl Med Mol Imaging. 2006 Jul;33 Suppl 1:44-53. doi: 10.1007/s00259-006-0135-1.
• Results Thorwarth D, Eschmann SM, Paulsen F, Alber M. Hypoxia dose painting by numbers: a planning study. Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):291-300. doi: 10.1016/j.ijrobp.2006.11.061.
• Results Lee NY, Mechalakos JG, Nehmeh S, Lin Z, Squire OD, Cai S, Chan K, Zanzonico PB, Greco C, Ling CC, Humm JL, Schoder H. Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):2-13. doi: 10.1016/j.ijrobp.2007.06.039. Epub 2007 Sep 14.
• Tandon S, Gupta M, Ahlawat P, Verma M, Nayak A, Bellige A, Chufal KS, Sethi JS, Pahuja A, Rai S, Singh A, Arora V, Yadav V, Simson DK, Ahmad I, Singh S, Vashisht D, Ansari A, Bansal R, Bhadri A, Vyas H, Mishra M, Saha R, Agarwal M, Chowdhary PS, Dewan AK, Gairola M. DEHyART trial: Study protocol for phase 2 randomised controlled study assessing the role of dose escalation using [18F] fluoromisonidazole positron emission tomography/computed tomography in head and neck cancers. Ecancermedicalscience. 2025 Jul 2;19:1937. doi: 10.3332/ecancer.2025.1937. eCollection 2025.

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