Hyperpolarized 129Xe Magnetic Resonance Imaging for Functional Avoidance Treatment Planning in Thoracic Radiation Therapy: A Comparison of Ventilation- and Gas Exchange-Guided Treatment Plans.

PURPOSE To present a methodology to use pulmonary gas exchange maps to guide functional avoidance treatment planning in radiation therapy (RT) and evaluate its efficacy compared with ventilation-guided treatment planning. METHODS AND MATERIALS Before receiving conventional RT for non-small cell lung cancer, 11 patients underwent hyperpolarized 129Xe gas exchange magnetic resonance imaging to map the distribution of xenon in its gas phase (ventilation) and transiently bound to red blood cells in the alveolar capillaries (gas exchange). Both ventilation and gas exchange maps were independently used to guide development of new functional avoidance treatment plans for every patient, while adhering to institutional dose-volume constraints for normal tissues and target coverage. Furthermore, dose-volume histogram (DVH)-based reoptimizations of the clinical plan, with reductions in mean lung dose (MLD) equal to the functional avoidance plans, were created to serve as the control group. To evaluate each plan (regardless of type), gas exchange maps, representing end-to-end lung function, were used to calculate gas exchange-weighted MLD (fMLD), gas exchange-weighted volume receiving ≥20 Gy (fV20), and mean dose in the highest gas exchanging 33% and 50% volumes of lung (MLD-f33% and MLD-f50%). Using each clinically approved plan as a baseline, the reductions in functional metrics were compared for ventilation-optimization, gas exchange optimization, and DVH-based reoptimization. Statistical significance was determined using the Freidman test, with subsequent subdivision when indicated by P values less than .10 and post hoc testing with Wilcoxon signed rank tests to determine significant differences (P < .05). Toxicity modeling was performed using an established function-based model to estimate clinical significance of the results. RESULTS Compared with DVH-based reoptimization of the clinically approved plans, gas exchange-guided functional avoidance planning more effectively reduced the gas exchange-weighted metrics fMLD (average ± SD, -78 ± 79 cGy for gas exchange, compared with -45 ± 34 cGy for DVH-based; P = .03), MLD-f33% (-135 ± 136 cGy, compared with -52 ± 47 cGy; P = .004), and MLD-f50% (-96 ± 95 cGy, compared with -47 ± 40 cGy; P = .01). Comparing the 2 functional planning types, gas exchange-guided planning more effectively reduced MLD-f33% compared with ventilation-guided planning (-64 ± 95; P = .009). For some patients, gas exchange-guided functional avoidance plans demonstrated clinically significant reductions in model-predicted toxicity, more so than the accompanying ventilation-guided plans and DVH-based reoptimizations. CONCLUSION Gas exchange-guided planning effectively reduced dose to high gas exchanging regions of lung while maintaining clinically acceptable plan quality. In many patients, ventilation-guided planning incidentally reduced dose to higher gas exchange regions, to a lesser extent. This methodology enables future prospective trials to examine patient outcomes.