Dosimetric risk factors for therapy‐related pneumonitis in patients with immunotherapy plus chemotherapy concurrent thoracic radiotherapy

Objective Combining immune checkpoint inhibitors (ICIs) with chemoradiotherapy is being actively investigated to improve clinical outcomes; however, this strategy may also increase the risk of treatment‐related toxicities. This multicenter study aimed to identify clinical and dosimetric predictors of treatment‐related pneumonitis (TRP) in this patient population, focusing on modifiable predictors of toxicity. Methods A retrospective review was conducted on 69 patients with lung or esophageal cancer treated at three hospitals. All patients received concurrent ICIs, chemotherapy, and thoracic radiotherapy at a dose of 50–60 Gy (in 2 Gy fractions) using inverse‐planned techniques. TRP was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Logistic regression modeling and receiver operating characteristic (ROC) analysis were employed for statistical evaluation. Results Any‐grade TRP occurred in 56.5% of patients. Grade 2–5 TRP occurred in 30.4%, 8.7%, 1.4%, and 0% of patients, respectively. Age ( p = 0.01; OR = 1.1) and mean lung dose (MLD) ( p = 0.02; OR = 2.4) independently contributed to the risk of any‐grade TRP. Age ( p = 0.03; OR = 1.1) and MLD ( p = 0.04; OR = 1.7) were also identified as risk factors for grade 2+ TRP. Other parameters, such as lung V 5, V 10, V 15, V 20, and V 30 were not significantly associated with TRP. ROC analysis identified 13.6 Gy as the optimal MLD threshold for predicting both any‐grade and grade 2+ TRP. Conclusions MLD and age were associated with a higher risk of TRP in patients receiving concurrent chemoradiotherapy and ICIs. These findings may help inform revisions to lung dose constraints, although validation in large‐scale prospective trials is warranted.