Dose-Volume Predictors of Radiation Pneumonitis After Thoracic Hypofractionated Radiation Therapy

Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis.

All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020. Tumors near critical structures (trachea, proximal tracheobronchial tree, esophagus, spinal cord, or heart) were considered central (within 2 cm), and those closer were classified as ultracentral (within 1 cm). The primary endpoint was grade ≥2 pneumonitis. Logistic regression analyses, adjusting for target size and dosimetric variables, were used to establish a dose threshold associated with <20% risk of grade ≥2 pneumonitis.

During a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the 2 dose regimens (17.3% vs 16.3%, P = .88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including 2 grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs 14.5%, P < .001), MLD (mean 13.0 Gy vs 9.5 Gy, P < .001), and lung V5 (mean 49.6% vs 40.6%, P = .01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 <17.7%, MLD <10.6 Gy, and V5 <41.3%. Multivariable analysis revealed a significant association between lung V20 and grade ≥2 pneumonitis (adjusted odds ratio, 1.48, P = .03).

To minimize the risk of grade ≥2 radiation pneumonitis when delivering 4 Gy per fraction at either 60 Gy or 72 Gy, it is advisable to maintain lung V20<17.7%. MLD <10.6 Gy and V5<41.3% can also be considered as lower-priority constraints. However, additional validation is necessary before incorporating these constraints into clinical practice or trial planning guidelines.