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.
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ICR Authors
Authors
Salem, A
Little, RA
Latif, A
Featherstone, AK
Babur, M
Peset, I
Cheung, S
Watson, Y
Tessyman, V
Mistry, H
Ashton, G
Behan, C
Matthews, JC
Asselin, M-C
Bristow, RG
Jackson, A
Parker, GJM
Faivre-Finn, C
Williams, KJ
O'Connor, JPB
Little, RA
Latif, A
Featherstone, AK
Babur, M
Peset, I
Cheung, S
Watson, Y
Tessyman, V
Mistry, H
Ashton, G
Behan, C
Matthews, JC
Asselin, M-C
Bristow, RG
Jackson, A
Parker, GJM
Faivre-Finn, C
Williams, KJ
O'Connor, JPB
Document Type
Journal Article
Date
2019-07-01
Date Accepted
2019-03-14
Abstract
PURPOSE: 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.
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (13), pp. 3818 - 3829
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1078-0432
eISSN
1557-3265
Collections
Research Team
Quantitative Biomedical Imaging