PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors have been shown to 
mitigate radiation-induced lung injury in preclinical models. The aim of this 
study was to evaluate whether ACE inhibitors decrease the risk of radiation 
pneumonitis in lung cancer patients receiving thoracic irradiation.
METHODS AND MATERIALS: Patients with Stage I through III small-cell and 
non-small-cell lung cancer treated definitively with radiation from 2004-2009 at 
the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively 
reviewed. Acute pulmonary toxicity was quantified within 6 months of completion 
of treatment according to the Common Terminology Criteria for Adverse Events 
version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, 
inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; 
dose-volume histogram parameters; and patient factors were assessed for 
association with Grade 2 or higher pneumonitis.
RESULTS: A total of 162 patients met the criteria for inclusion. The majority of 
patients had Stage III disease (64%) and received concurrent chemotherapy (61%). 
Sixty-two patients were identified as ACE inhibitor users (38%). All patients 
had acceptable radiation plans based on dose-volume histogram constraints (V20 
[volume of lung receiving at least 20 Gy] ≤37% and mean lung dose ≤20 Gy) with 
the exception of 2 patients who did not meet both criteria. Grade 2 or higher 
pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher 
pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 
0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in 
patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 
(volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 
0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung 
receiving at least 30 Gy), and mean lung dose were not independently associated 
with Grade 2 or higher pneumonitis.
CONCLUSION: ACE inhibitors may decrease the incidence of radiation pneumonitis 
in patients receiving thoracic radiation for lung cancer. These findings are 
consistent with preclinical evidence and should be prospectively evaluated.