Risk Factors for Pneumonitis Induced by Combined Radiotherapy and Immunotherapy: A Multicenter Prospective Study.

Abstract

Background: The combination of radiotherapy (RT) and immune checkpoint inhibitors (ICIs) has become an important therapeutic approach for lung cancer. However, pneumonitis remains a major treatment-related toxicity of this therapeutic approach, and the risk factors for pneumonitis associated with combined RT and ICIs under different treatment sequences have not been clearly defined.

Patients and methods: Patients with lung cancer who received thoracic RT were prospectively enrolled from 3 centers. Pneumonitis was assessed according to CTCAE version 4.0 by a multidisciplinary team. Cox proportional hazards models were used to identify factors associated with pneumonitis.

Results: During a median follow-up of 28.2 months, 133 of 380 (35.0%) patients developed symptomatic pneumonitis (grade ≥2). Treatment with ICIs was associated with an increased risk of symptomatic pneumonitis (hazard ratio [HR], 1.69; 95% CI, 1.20-2.39; P=.003). Among 170 patients treated with ICIs, 89 received ICIs before RT (ICI-first group) and 81 received ICIs after RT (RT-first group). In the ICI-first group, 42 (47.2%) patients developed symptomatic pneumonitis, and an interval of <21 days between ICI administration and RT and a higher percentage of lung volume receiving ≥20 Gy (V20) were associated with an increased risk of pneumonitis. In the RT-first group, 32 (39.5%) patients developed symptomatic pneumonitis, with older age and higher V20 identified as risk factors.

Conclusions: Administration of ICIs before RT significantly increases the risk of pneumonitis in patients receiving thoracic RT. The dosimetric factor V20 consistently emerged as a key determinant of pneumonitis risk in both the ICI-first and RT-first groups. These findings aid in preventing the occurrence of pneumonitis induced by combined RT and ICIs, thereby improving patients' quality of life and survival outcomes.