{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:58:27Z","timestamp":1780599507414,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: We evaluated the utility of HNSCC LN R2* relaxation times to infer the oxygenation status of LN non-invasively at baseline and when breathing air and 100% oxygen to predict chemoradiotherapeutic locoregional response at 2 years. Hypoxia within LNs has been associated with poorer outcomes following CRT. Deoxyhaemoglobin decreases MRI transverse relaxation time (T2*) (lengthening inverse, R2*). Methods: A total of 54 patients underwent 1.5T-MRI before CRT. Conventional MR sequences were supplemented with T2* sequences breathing both air and 100% oxygen; pathological nodes identified in consensus were volumetrically contoured to T2* parametric maps. Results: Patients followed-up with for &gt;2 years were categorised by multidisciplinary consensus into post-therapy complete local response (CR; n = 32\/54) and local nodal disease relapse (RD; n = 22\/54). Our data demonstrated, by R2*, that nodes that sustained post-therapy CR are significantly more hypoxic compared with relapsing nodes and paradoxically demonstrate a significant increase in hypoxia on 100% oxygen. Pre-treatment LN short axis diameter, various qualitative descriptors of malignancy, and quantitative DWI were not useful in discriminating successful response to CRT. Conclusions: This study demonstrates that a significant differential response to 100% oxygen and higher baseline R2* LN measurements could be exploited in risk stratification prior to CRT, and future work could be directed towards understanding the contrast mechanisms of R2* imaging, underpinning the observed differences in the context of hypoxia.<\/jats:p>","DOI":"10.3390\/cancers17142333","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T08:04:41Z","timestamp":1752566681000},"page":"2333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxygen-Enhanced R2* Weighted MRI and Diffusion Weighted MRI of Head and Neck Squamous Cell Cancer Lymph Nodes in Prediction of 2-Year Outcome Following Chemoradiotherapy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3564-3383","authenticated-orcid":false,"given":"Harbir Singh","family":"Sidhu","sequence":"first","affiliation":[{"name":"Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK"},{"name":"Imaging Department, University College London Hospitals, 235 Euston Road, Ground Floor North, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Price","sequence":"additional","affiliation":[{"name":"Medical Physics and Biomedical Engineering, University College London Hospitals, 235 Euston Road, Basement, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Beale","sequence":"additional","affiliation":[{"name":"Imaging Department, University College London Hospitals, 235 Euston Road, Ground Floor North, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Morley","sequence":"additional","affiliation":[{"name":"Imaging Department, University College London Hospitals, 235 Euston Road, Ground Floor North, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-8754","authenticated-orcid":false,"given":"Sola","family":"Adeleke","sequence":"additional","affiliation":[{"name":"Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianthi-Vasiliki","family":"Papoutsaki","sequence":"additional","affiliation":[{"name":"Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-290X","authenticated-orcid":false,"given":"Martin","family":"Forster","sequence":"additional","affiliation":[{"name":"Department of Oncology, University College London, UCL Cancer Institute, Paul O\u2019Gorman Building, 72 Huntley Street, London WC1E 6DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2898-3219","authenticated-orcid":false,"given":"Dawn","family":"Carnell","sequence":"additional","affiliation":[{"name":"Radiotherapy Department, University College London Hospitals, 235 Euston Road, Basement Floor, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruheena","family":"Mendes","sequence":"additional","affiliation":[{"name":"Radiotherapy Department, University College London Hospitals, 235 Euston Road, Basement Floor, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart Andrew","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK"},{"name":"Imaging Department, University College London Hospitals, 235 Euston Road, Ground Floor North, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shonit","family":"Punwani","sequence":"additional","affiliation":[{"name":"Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK"},{"name":"Imaging Department, University College London Hospitals, 235 Euston Road, Ground Floor North, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/1097-0142(19940101)73:1<187::AID-CNCR2820730132>3.0.CO;2-J","article-title":"Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor","volume":"73","author":"Leemans","year":"1994","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/jnci\/88.13.890","article-title":"Larynx preservation in pyriform sinus cancer: Preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group","volume":"88","author":"Lefebvre","year":"1996","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.radonc.2011.05.036","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site","volume":"100","author":"Blanchard","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1001\/jamaoto.2013.5988","article-title":"Quality of life among long-term survivors of head and neck cancer treated by intensity-modulated radiotherapy","volume":"140","author":"Chen","year":"2014","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0360-3016(00)00415-6","article-title":"Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: A comparison limited to patients eligible for surgery","volume":"47","author":"MacKenzie","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.canep.2015.02.004","article-title":"Clinical features and prognostic factors in patients with head and neck cancer: Results from a multicentric study","volume":"39","author":"Leoncini","year":"2015","journal-title":"Cancer Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4132","DOI":"10.1200\/JCO.2016.68.2955","article-title":"Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx","volume":"34","author":"Chakravarthy","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ejrad.2007.02.037","article-title":"Detection of lymph node metastases in head and neck cancer: A meta-analysis comparing US, USgFNAC, CT and MR imaging","volume":"64","author":"Bondt","year":"2007","journal-title":"Eur. J. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s00330-008-1187-3","article-title":"Morphological MRI criteria improve the detection of lymph node metastases in head and neck squamous cell carcinoma: Multivariate logistic regression analysis of MRI features of cervical lymph nodes","volume":"19","author":"Nelemans","year":"2009","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jinorgbio.2013.12.010","article-title":"Oxygen sensing strategies in mammals and bacteria","volume":"133","author":"Taabazuing","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_12","first-page":"1454","article-title":"A dynamic model of the hypoxia-inducible factor 1 (HIF-1) network","volume":"126","author":"Nguyen","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1148\/83.2.328","article-title":"Demonstration of an anoxic component in mouse tumour cell population by in vivo assay of survival following irradiation","volume":"83","author":"Powers","year":"1964","journal-title":"Radiology"},{"key":"ref_14","first-page":"439","article-title":"A new method for the bed-side recording of tissue pO2 histograms","volume":"90","author":"Fleckenstein","year":"1984","journal-title":"Verh. Dtsch. Ges. Inn. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1001\/archotol.1994.01880270031006","article-title":"Oxygen tension measurements of head and neck cancers","volume":"120","author":"Terris","year":"1994","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.radonc.2005.06.038","article-title":"Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study","volume":"77","author":"Nordsmark","year":"2005","journal-title":"Radiother. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1097\/00005537-200005000-00001","article-title":"Head and neck cancer: The importance of oxygen","volume":"110","author":"Terris","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_18","first-page":"297","article-title":"Tumor hypoxia in cancer therapy","volume":"435","author":"Brown","year":"2007","journal-title":"Methods Enzymol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/jmri.1880070134","article-title":"Effect of oxygen inhalation on relaxation times in various tissues","volume":"7","author":"Tadamura","year":"1997","journal-title":"J. Magn. Reason. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1007\/s00330-014-3167-0","article-title":"Blood oxygenation level-dependent MR imaging as a predictor of therapeutic response to concurrent chemoradiotherapy in cervical cancer: A preliminary experience","volume":"24","author":"Kim","year":"2014","journal-title":"Eur. Radiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00066-009-1870-6","article-title":"Monitoring of tumor oxy- genation changes in head-and-neck carcinoma patients breathing a hyperoxic hypercapnic gas mixture with a noninvasive MRI technique","volume":"185","author":"Kotas","year":"2009","journal-title":"Strahlenther. Onkol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jmri.24837","article-title":"Value of R2* obtained from T2*-weighted imaging in predicting the prognosis of advanced cervical squamous carcinoma treated with concurrent chemoradiotherapy","volume":"42","author":"Li","year":"2015","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1053\/srao.2001.18104","article-title":"Magnetic resonance imaging for in vivo assessment of tissue oxygen concentration","volume":"11","author":"Krishna","year":"2001","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3174\/ajnr.A3070","article-title":"Imaging brain oxygenation with MRI using blood oxygenation approaches: Methods, validation, and clinical applications","volume":"34","author":"Christen","year":"2013","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/jmri.25134","article-title":"Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T","volume":"44","author":"Panek","year":"2016","journal-title":"J. Magn. Reason. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/jmri.23891","article-title":"Blood oxy- genation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: A pilot study","volume":"37","author":"Jiang","year":"2013","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1148\/radiol.091669","article-title":"Science to practice: What does MR oxygenation imaging tell us about human breast cancer hypoxia?","volume":"254","author":"Padhani","year":"2010","journal-title":"Radiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40644-016-0080-6","article-title":"I for the prediction of treatment response in head and neck squamous cell carcinoma: Potential and limitations","volume":"16","author":"King","year":"2016","journal-title":"Cancer Imaging"},{"key":"ref_29","unstructured":"Edge, S.B., Byrd, D.R., Compton, C.C., Fritz, A.G., Greene, F.L., and Trotti, A. (2009). American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Springer. [7th ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s41747-024-00429-1","article-title":"Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting","volume":"8","author":"McCabe","year":"2024","journal-title":"Eur. Radiol. Exp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/mrm.10283","article-title":"Real-time quantification of T2* changes using multiecho planar imaging and numerical methods","volume":"48","author":"Hagberg","year":"2002","journal-title":"Magn. Reson. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/mrm.21342","article-title":"Oxygenation and hematocrit dependence of transverse relaxation rates of blood at 3T","volume":"58","author":"Zhao","year":"2007","journal-title":"Magn. Reson. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1088\/0031-9155\/49\/15\/006","article-title":"Physiological noise in murine solid tumors using T2*-weighted gradient- echo imaging: A marker of tumor acute hypoxia?","volume":"49","author":"Baudelet","year":"2004","journal-title":"Phys. Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/S0360-3016(02)02825-0","article-title":"Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging","volume":"53","author":"Rijpkema","year":"2002","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/mrm.1118","article-title":"In vivo BOLD contrast MRI mapping of subcutaneous vascular function and matura- tion: Validation by intravital microscopy","volume":"45","author":"Neeman","year":"2001","journal-title":"Magn. Reson. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0360-3016(98)00038-8","article-title":"Correlation of magnetic resonance and oxygen microelectrode measurements of carbogen-induced changes in tumour oxygenation","volume":"41","author":"River","year":"1998","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0730-725X(98)00088-5","article-title":"Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: Application to human muscle study","volume":"16","author":"Lebon","year":"1998","journal-title":"Magn. Reson. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/nbm.716","article-title":"Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours","volume":"14","author":"Howe","year":"2001","journal-title":"NMR Biomed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1148\/radiol.2541090395","article-title":"Intrinsic susceptibility MR imaging of chemically-induced rat mammary tumors: Relationship to histological assessment of hypoxia and fibrosis","volume":"254","author":"McPhail","year":"2009","journal-title":"Radiology"},{"key":"ref_40","unstructured":"Padhani, A.R., Ah-See, M.L.W., Taylor, N.J., Stirling, J.J., and Daley, F.M. (2005, January 7\u201313). An investigation of histological and DC-MRI correlates of intrinsic susceptibility contrast relaxivity (R2*) in human breast cancer [abstr]. Proceedings of the Thirteenth Meeting of the International Society for Magnetic Resonance in Medicine, Miami Beach, FL, USA."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/sj.bjc.6604903","article-title":"Carbogen breathing increases prostate cancer oxygenation: A translational MRI study in murine xenografts and humans","volume":"100","author":"Alonzi","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.ijrobp.2007.01.018","article-title":"Hypoxia in prostate cancer: Correlation of BOLD-MRI with pimonidazole immuno- histochemistry: Initial observations","volume":"68","author":"Hoskin","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1158\/1078-0432.CCR-08-1287","article-title":"Diffusion-weighted magnetic resonance imaging for predicting and detecting early response to chemoradiation therapy of squamous cell carcinomas of the head and neck","volume":"15","author":"Kim","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1148\/radiol.12120167","article-title":"Head and neck squamous cell carcinoma: Diagnostic performance of diffusion-weighted MR imaging for the prediction of treatment response","volume":"266","author":"King","year":"2013","journal-title":"Radiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/RLU.0b013e318248524a","article-title":"FDG PET\/CT and diffusion-weighted imaging of head and neck squamous cell carcinoma: Comparison of prognostic significance between primary tumor standardized uptake value and apparent diffusion coefficient","volume":"37","author":"Nakajo","year":"2012","journal-title":"Clin. Nucl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3174\/ajnr.A4114","article-title":"Diffusion-weighted imaging of the head and neck in healthy subjects: Reproducibility of ADC values in different MRI systems and repeat sessions","volume":"36","author":"Pouwels","year":"2015","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_47","first-page":"5522","article-title":"Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma","volume":"56","author":"Kimura","year":"1996","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/14\/2333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:38Z","timestamp":1760033378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/14\/2333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":47,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cancers17142333"],"URL":"https:\/\/doi.org\/10.3390\/cancers17142333","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]}}}