Oxygen-enhanced MRI in patients with uterine cervical carcinoma: feasibility and treatment-associated changes in tumour oxygen-enhanced response

Anubhav Datta, Michael J. Dubec, Michael Berks, Ross A. Little, Lisa Barraclough, Kate Haslett, Nuria Porta, Prakash Manoharan, David L. Buckley, Catharine West, Ananya Choudhury, Peter Hoskin, James P.B. O’Connor

Purpose Tumour hypoxia causes resistance against radiotherapy and chemotherapy in locally advanced cervical cancer (LACC). Non-invasive magnetic resonance imaging (MRI) biomarkers have the potential to guide hypoxia-targeted therapy but require technical development and validation. This study evaluated the feasibility and early treatment response monitoring capabilities of oxygen-enhanced MRI (OE-MRI) in healthy female volunteers and patients with LACC. Methods Healthy volunteers underwent OE-MRI to demonstrate the feasibility of the technique and to compare the onset, magnitude, and duration of change in longitudinal relaxation rate (Δ R 1 ) for breathing either 100% oxygen or carbogen. Uterine cervix and body tissues were examined. Next, patients with biopsy-proven LACC underwent OE-MRI pre-treatment, and then, at 3 and 5 weeks into chemotherapy, it was combined with external beam radiotherapy. Results Feasibility was demonstrated in 97% (31/32) of uterine tissue regions of interest, measured in 18 volunteers. Δ R 1 values in the uterine cervix and body were similar across gas types with a cohort Δ R 1 of between 0.026 and 0.033 s −1 . In patients with LACC, significant increases in tumour Δ R 1 were observed during treatment by week 3 (mean increase, 0.0143 s −1 ; 95% CI 0.0014 to 0.0273; p = 0.035). At week 5, six of eight evaluable patients showed a >50% treatment-associated increase in tumour Δ R 1 . Changes persisted in most patients to the end of treatment. Conclusion This first dedicated OE-MRI study in cervical cancer shows technique feasibility in healthy volunteers and patients with LACC. Treatment-associated increases in tumour Δ R 1 were demonstrated during chemoradiotherapy and likely reflect hypoxia modification. These findings support further evaluation of OE-MRI alongside independent hypoxia biomarkers in larger cervical cancer cohorts.