title: Do angiotensin-converting enzyme inhibitors reduce the risk of symptomatic radiation pneumonitis in patients with non-small cell lung cancer after definitive radiation therapy? Analysis of a single-institution database.
abstract: OBJECTIVE
  Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP.
  
  
  RESULTS
  Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04).
  
  
  CONCLUSIONS
  A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Quynh-Nhu
authors.initials: QN
authors.lastname: Nguyen
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Levy
authors.forename: Michael
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Gold
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D017706:Lisinopril / Q000627:therapeutic use; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017564:Radiation Pneumonitis / Q000517:prevention & control*; D012189:Retrospective Studies; D012306:Risk; D012737:Sex Factors; D013777:Tetrazoles / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D000068756:Valsartan; C437965:olmesartan; D017706:Lisinopril; D014633:Valine