The combination of immune checkpoint inhibitors (ICIs) with radiotherapy (RT) has improved survival in patients with advanced lung cancer, yet treatment-related pneumonitis (TRP) is highly toxic. Current limitations include the absence of robust risk stratification models for TRP and unclear safety criteria for ICI rechallenge, hindering the management of recurrent TRP (rTRP). In this multicenter retrospective study, we analyzed 262 lung cancer patients receiving radioimmunotherapy. The data included baseline demographics, immunotherapy regimens, and radiotherapy parameters. TRP was graded per CTCAE v5.0. Univariate and multivariate logistic regression identified predictors of TRP and rTRP severity. The incidence of TRP is 57.6% (151/262), with grade 1, 2, and ≥ 3 TRP occurring in 24.4%, 25.6%, and 7.6% of patients, respectively. The median time to TRP onset is 113 days (IQR, 73–155). Multivariate analysis reveals PD-1 inhibitors and ICI cycle number as predictors of G ≥ 1 TRP, whereas Dmean predicts all grades. Dose‒response modeling reveals Dmean thresholds for 50% TRP risk: 8.7 Gy (G ≥ 1), 15.3 Gy (G ≥ 2), and 23.4 Gy (G ≥ 3). Among the 53 patients receiving ICI rechallenge, 25.4% (13/53) developed rTRP. Rechallenge within 4 weeks significantly increases rTRP risk (OR, 0.061; 95% CI, 0.010–0.368; P = 0.002). Dmean serves as a continuous risk modifier for TRP severity, with Dmean > 15.3 Gy associated with grade ≥ 2 toxicity. An interval of ≥ 4 weeks after TRP is proposed as a safety window for ICI rechallenge, addressing critical gaps in radioimmunotherapy toxicity management. Patients with advanced lung cancer who receive both radiotherapy and immunotherapy may develop a serious side effect known as treatment-related pneumonitis. We analyzed data from 262 lung cancer patients who underwent both treatments at two hospitals and found that the mean radiation dose to the lungs is a key predictor of pneumonitis. For instance, when this dose reaches 15.3 Gy, half of the patients develop moderate or more severe pneumonitis. Additionally, if immunotherapy is resumed within less than 4 weeks after the onset of pneumonitis, the risk of recurrence increases significantly. These findings offer potential guidance to help clinicians improve treatment decisions. Ruan, Fang, Sun et al., analyze treatment-related pneumonitis (TRP) in lung cancer patients receiving radioimmunotherapy. They find that the mean lung dose can serve as a continuous predictor of TRP severity and a ≥ 4-week interval as a safety window for reducing recurrence risk upon immunotherapy rechallenge.
Ruan et al. (Thu,) studied this question.