Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer

OBJECTIVE: In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients. MATERIALS AND METHODS: Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram <−950, RA(950)) were measured. Patients were classified into three subgroups based on qualitative and quantitative COPD and tumour-specific imaging phenotypes: (1) tumour-specific ventilation defects (TSD), (2) tumour-specific and other ventilation defects without emphysema (TSD(V)), and, (3) tumour-specific and other ventilation defects with emphysema (TSD(VE)). RESULTS: Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV(1) = 77%(pred)) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = .02) and FEV(1)/FVC (p = .04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA(950), p < .001). There were significant relationships for whole-lung VDP (p < .05), but not RECIST or tumour-lobe VDP measurements with pulmonary function and exercise measurements. Preliminary analysis for non-tumour burden ventilation abnormalities using Reader-operator-characteristic (ROC) curves reflected a 94% classification rate for smoking pack-years, 93% for FEV(1)/FVC and 82% for RA(950). ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV(1)/FVC (0.92/0.80/4.6/0.3), RA(950) (0.92/0.80/4.6/0.3) and RECIST (0.58/0.80/2.9/1.1). CONCLUSIONS: In this prospectively planned interim-analysis of a larger clinical trial, NSCLC patients were classified based on COPD imaging phenotypes. A proof-of-concept evaluation showed that FEV(1)/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy.