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

Objectives: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Clinical relevance statement: 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.

Key points: 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.