Comprehensive Pneumonitis Profile of Thoracic Radiotherapy Followed by Immune Checkpoint Inhibitor and Risk Factors for Radiation Recall Pneumonitis in Lung Cancer

Abstract

PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and MaterialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

“…Radiotherapy is one of the major methods of local treatment for thoracic tumors, but the occurrence of RP limits the effective radiation dose. Studies have shown that the incidence of RP is 15.5–36% [ 47 ], which makes it a serious complication in the treatment of thoracic tumors. In recent years, there are numerous studies about the mechanisms of radiation-induced lung injury (RILI), each focusing on specific cell types, such as endothelial cells, T helper cells, as well as fibroblasts.…”

Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments

“…Lu et al [ 112 ] also identify the time factor as a fundamental element for differential diagnosis. In their cohort, the overall rates of different types of pneumonia were, respectively, 8.2% (n = 16) CIP, 46.9% (n = 92) RP and 7.1% (n = 14) RRP.…”

“…RRP was defined as inflammatory reactions in previously irradiated fields on chest CT after ICI administration and more than 6 months after TRT. As far as CT characteristics are concerned, the most characteristic results concern CIP with the finding of diffuse patches (47.4%), consolidation (26.3%) and ground-glass opacity (26.3%), unlike RP and RRP pneumonias which have similar chest CT with consolidation-type lesions and streaks within the irradiation field [ 112 ].…”

A dynamic nomogram predicting symptomatic pneumonia in patients with lung cancer receiving thoracic radiation

“…Previous studies have shown that clinical factors such as older age, T stage, female, non-smokers, ECOG performance [ 3 , 4 ], tumor location in the mid-lower lung, chemotherapy, targeted therapies, immune checkpoint inhibitors (ICIs), postoperative radiotherapy (PORT), total lung volume, smaller spared lung volume, and poor pulmonary function are closely related to RP incidence [ 3 , 7 – 13 ]. Additionally, whole lung V5, V10, V20, mean lung dose (MLD), and normal tissue complication probability (NTCP) have been reported to be strongly associated with RP occurrence [ 14 – 16 ].…”