Oxygen-enhanced MRI is feasible, repeatable, and detects radiotherapy-induced change in hypoxia in xenograft models and in patients with non-small cell lung cancer
Bristow, Robert G
O'Connor, James PB
AffiliationDivision of Cancer Sciences, University of Manchester, Manchester, United Kingdom
MetadataShow full item record
AbstractPurpose: Hypoxia is associated with poor prognosis and is predictive of poor response to cancer treatments, including radiotherapy. Developing noninvasive biomarkers that both detect hypoxia prior to treatment and track change in tumor hypoxia following treatment is required urgently.Experimental Design: We evaluated the ability of oxygen-enhanced MRI (OE-MRI) to map and quantify therapy-induced changes in tumor hypoxia by measuring oxygen-refractory signals in perfused tissue (perfused Oxy-R). Clinical first-in-human study in patients with non-small cell lung cancer (NSCLC) was performed alongside preclinical experiments in two xenograft tumors (Calu6 NSCLC model and U87 glioma model).Results: MRI perfused Oxy-R tumor fraction measurement of hypoxia was validated with ex vivo tissue pathology in both xenograft models. Calu6 and U87 experiments showed that MRI perfused Oxy-R tumor volume was reduced relative to control following single fraction 10-Gy radiation and fractionated chemoradiotherapy (P < 0.001) due to both improved perfusion and reduced oxygen consumption rate. Next, evaluation of 23 patients with NSCLC showed that OE-MRI was clinically feasible and that tumor perfused Oxy-R volume is repeatable [interclass correlation coefficient: 0.961 (95% CI, 0.858-0.990); coefficient of variation: 25.880%]. Group-wise perfused Oxy-R volume was reduced at 14 days following start of radiotherapy (P = 0.015). OE-MRI detected between-subject variation in hypoxia modification in both xenograft and patient tumors.Conclusions: These findings support applying OE-MRI biomarkers to monitor hypoxia modification, to stratify patients in clinical trials of hypoxia-modifying therapies, to identify patients with hypoxic tumors that may fail treatment with immunotherapy, and to guide adaptive radiotherapy by mapping regional hypoxia.
CitationSalem A, Little RA, Latif A, Featherstone AK, Babur M, Peset I, et al.Oxygen-enhanced MRI is feasible, repeatable, and detects radiotherapy-induced change in hypoxia in xenograft models and in patients with non-small cell lung cancer. Clin Cancer Res. 2019.
JournalClinical Cancer Research
- Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.
- Authors: Little RA, Jamin Y, Boult JKR, Naish JH, Watson Y, Cheung S, Holliday KF, Lu H, McHugh DJ, Irlam J, West CML, Betts GN, Ashton G, Reynolds AR, Maddineni S, Clarke NW, Parker GJM, Waterton JC, Robinson SP, O'Connor JPB
- Issue date: 2018 Sep
- Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.
- Authors: O'Connor JP, Boult JK, Jamin Y, Babur M, Finegan KG, Williams KJ, Little RA, Jackson A, Parker GJ, Reynolds AR, Waterton JC, Robinson SP
- Issue date: 2016 Feb 15
- Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.
- Authors: Linnik IV, Scott ML, Holliday KF, Woodhouse N, Waterton JC, O'Connor JP, Barjat H, Liess C, Ulloa J, Young H, Dive C, Hodgkinson CL, Ward T, Roberts D, Mills SJ, Thompson G, Buonaccorsi GA, Cheung S, Jackson A, Naish JH, Parker GJ
- Issue date: 2014 May
- Data-driven mapping of hypoxia-related tumor heterogeneity using DCE-MRI and OE-MRI.
- Authors: Featherstone AK, O'Connor JPB, Little RA, Watson Y, Cheung S, Babur M, Williams KJ, Matthews JC, Parker GJM
- Issue date: 2018 Apr
- Metabolic targeting of HIF-dependent glycolysis reduces lactate, increases oxygen consumption and enhances response to high-dose single-fraction radiotherapy in hypoxic solid tumors.
- Authors: Leung E, Cairns RA, Chaudary N, Vellanki RN, Kalliomaki T, Moriyama EH, Mujcic H, Wilson BC, Wouters BG, Hill R, Milosevic M
- Issue date: 2017 Jun 15