Measuring repeatability of dynamic contrast-enhanced MRI biomarkers improves evaluation of biological response to radiotherapy in lung cancer.

Abstract

To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response. A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (K^trans), extravascular extracellular space volume fraction (v_e) and plasma volume fraction (v_p) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation. Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for v_p, which was 42.44%. Cohort-level changes were significant for K^trans and v_e (p < 0.001) and tumour volume (p = 0.002). K^trans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in v_e despite the cohort-level change. Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies. Dynamic contrast-enhanced magnetic resonance imaging biomarkers K^trans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics. Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.