First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema.

ABSTRACT

PURPOSE: Only a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that stereotactic ablative radiation therapy of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and secondarily explore the efficacy of stereotactic irradiation for lung volume reduction (SILVR) over 18 months after intervention in patients with severe emphysema. METHODS AND MATERIALS We conducted a single-arm, prospective clinical trial in eligible patients with severe emphysema treated with unilateral stereotactic ablative radiation therapy (45 Gy in 3 fractions) to a target within the most emphysematous region. The primary outcome was safety in terms of incidence of grade ≥3 adverse events, and the secondary outcome was efficacy. RESULTS: Eight patients received the intervention. Median (range) baseline characteristics were age 73 years (63-78); forced expiratory volume in 1 second percent of predicted value (FEV1%) 28.5% (19.0-42.0); diffusing capacity of the lungs for carbon monoxide percent of predicted value 40% (24.0-67.0); and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index 5.5 (5-9). The incidence of grade ≥3 adverse events was 3 of 8 (37.5%). The relative change in target lobe volume was -23.1% (-1.6 to -41.5) and -26.5% (-20.6 to -40.8) at 6 and 18 months, respectively. The absolute ΔFEV1% was greater in patients with a BODE index ≤5 versus ≥6 (+12.0% vs -2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V60BED3) correlated with the absolute change in target lobe volume at 18 months. CONCLUSIONS: SILVR appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe and effective in patients with a lower BODE index and/or less parenchymal destruction.