Decreased Risk of Radiation Pneumonitis with Coincident Concurrent Use of ACE Inhibitors in Lung SBRT

1. Decreased Risk of Radiation Pneumonitis With Coincident Concurrent Use Of Angiotensin-Converting Enzyme Inhibitors In Patients Receiving Lung Stereotactic Body Radiation Therapy (SBRT) Fiori Alite, M. Surucu, I. Mescioglu, M. Harkenrider Loyola University Medical Center, Maywood, IL

2. Introduction • Angiotensin Converting Enzymes have demonstrated efficacy in preclinical models of ameliorating lung radiation toxicity • 4 Retrospective reviews have demonstrated conflicting results in terms of documenting improvement of symptomatic radiation pneumonitis • RTOG 0123 was initiated to test efficacy of the ACEi captopril to decrease rates of symptomatic pneumonitis in patients treated with radiation for locally advanced non-small cell and small cell lung carcinoma • To our knowledge, effect of concurrent ACEi use in patients treated with lung SBRT has not been tested • The objective of this study was to evaluate retrospectively the role of concurrent incidental use of ACE inhibitors in ameliorating development of symptomatic acute lung toxicity in the setting of thoracic SBRT.

3. Materials and Methods • A retrospective review of patients treated with thoracic SBRT analyzing rates of incidental concurrent use of ACEi and development of symptomatic pneumonitis was performed. • We analyzed 193 patients treated with Linac-based SBRT with for primary, recurrent and metastatic lung tumors. Patients were treated with doses of 40-60Gy in 3-5 fractions from 2006 to 2013. • These plans were evaluated to meet RTOG 0236 criteria for dose coverage and lung tolerance. • We recorded symptomatic pneumonitis up to 6 months post treatment based on Common Terminology Criteria for Adverse Events Version 4.0. • Pre and post treatment medication profiles were reviewed to document use of ACE inhibitors, angiotensin receptor blockers, bronchodilators, ASA, PDE5 inhibitors, nitrates and endothelin receptor antagonists. A decision tree analysis was performed to investigate the risk factors for development of symptomatic pneumonitis. • Patient age, sex, KPS, clinical stage, tumor location, prescription dose, and concurrent use of 7 different bronchoactive medications were used to train this decision tree.

4. Results • The majority (85%) of patients were treated with 50Gy in 5 fractions, and 8% of patients with 60Gy in 5 fraction. • Twenty three patients experienced Grade 2 or higher pneumonitis, an absolute rate of 11.9%. • Forty-eight patients (24.9%) were found to be on ACEi during delivery of SBRT. • Only one patient on a concurrent ACEi experienced symptomatic pneumonitis. • The rate of Grade 2 or higher pneumonitis was significantly lower in patients prescribed an ACEi vs. patients not on an ACEi (2% vs. 15%, χ2 test p = 0.01). • Additionally, in a decision tree analysis accounting for the clinical/patient characteristics and medication profiles we can predict with 92% accuracy that patients on an ACEi will not experience symptomatic pneumonitis.

5. Patient Characteristics

6. Decision Tree Analysis No 47/1

7. Conclusions • ACEi appear to have efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung stereotactic body radiation therapy which was validated in a decision tree statistical analysis. • With the advent of increased lung cancer screening as well as expanding clinical practice of treating lung oligometastases, identifying toxicity modifiers in this population with often compromised lung function is important. • This is of particular concern in patients that are receiving several courses of radiation to the chest, or patients treated to multiple sites and overall greater lung volume. • Prospective analysis is needed to confirm these findings.

8. References