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

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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<inf>950</inf>) 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<inf>V</inf>), and, (3) tumour-specific and other ventilation defects with emphysema (TSD<inf>VE</inf>). Results: Seventeen stage-III NSCLC patients were evaluated (68±7 years, 7M/10F, mean FEV<inf>1</inf>=77%<inf>pred</inf>) 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<inf>1</inf>/FVC (p=04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA<inf>950</inf>, 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<inf>1</inf>/FVC and 82% for RA<inf>950</inf>. ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV<inf>1</inf>/FVC (0.92/0.80/4.6/0.3), RA<inf>950</inf> (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<inf>1</inf>/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy.




Sheikh, K., Capaldi, D. P. I., Hoover, D. A., Palma, D. A., Yaremko, B. P., & Parraga, G. (2015). Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer. European Journal of Radiology Open, 2, 81–89.

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