title: Angiotensin-converting enzyme inhibitors decrease the risk of radiation pneumonitis after stereotactic body radiation therapy.
abstract: OBJECTIVE
  Although angiotensin-converting enzyme (ACE) inhibitor use during conventionally fractionated radiation therapy has been associated with a decreased risk of radiation pneumonitis (RP), a similar effect has not been demonstrated in stereotactic body radiation therapy (SBRT). The purpose of this study was to examine the impact of ACE inhibitor use during SBRT on the risk of symptomatic (grade ≥2) RP.
  
  
  METHODS
  Patients with at least 1 follow-up treated with SBRT for primary lung cancer were included. ACE inhibitors, angiotensin receptor blockers, statins, nonsteroidal anti-inflammatory drugs, and glucocorticoids were examined. RP was determined from all available medical records, including follow-up appointments with radiation oncology, pulmonology, medical oncology, and hospitalizations. It was scored with the Common Terminology Criteria for Adverse Events, version 4.0. Analysis was performed with Kaplan-Meier and Cox proportional hazards modeling.
  
  
  RESULTS
  A total of 257 patients met inclusion criteria. Seventy (27.2%) used an ACE inhibitor during SBRT. The overall rates of grade ≥2 and ≥3 RP were 19.1% (n = 49) and 7.0% (n = 18), respectively. ACE inhibitor users experienced greater freedom from symptomatic RP on univariate (vs nonusers, 89.8% vs 76.3% at 12 months, P = .029) and multivariate analysis (hazard ratio 0.373, 95% confidence interval 0.156-0.891, P =.026). The volume of normal lung tissue receiving ≥5 Gy, %, ≥10 Gy, ≥20 Gy, and mean lung dose were also significantly associated with RP on univariate and multivariate analysis. ACE inhibitor use was not associated with overall survival. Angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, glucocorticoids, and statin administration were not associated with symptomatic RP or survival.
  
  
  CONCLUSIONS
  ACE inhibitor use during SBRT was associated with significantly greater freedom from grade ≥2 RP, even after adjusting for pulmonary dose. Given the data on their protective effect in human and animal models, a prospective evaluation is warranted.
authors.affiliation: Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Harder
authors.affiliation: Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
authors.forename: Henry S
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
authors.forename: Sameer K
authors.initials: SK
authors.lastname: Nath
authors.affiliation: Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Mancini
authors.affiliation: Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut. Electronic address: roy.decker@yale.edu.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Decker
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012307:Risk Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors