Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are increasingly used to treat advanced cancers. Despite data indicating exaggerated radiation toxicities in patients with autoimmune disease, the safety of thoracic radiotherapy in patients with prior ICI-associated immune-related adverse events (irAEs) is undefined.
Patients and methods
Patients treated from 2014-2020 with ICIs were queried for receipt of corticosteroids and radiotherapy. Patients who received thoracic radiation after symptomatic irAEs were assessed for ≥ grade 2 radiation pneumonitis (RP). Characteristics predictive of RP were assessed using logistic regression and response-relationships were modeled.
Among 496 assessed patients, 41 with irAE history subsequently treated with thoracic radiotherapy were analyzed. Most irAEs were grade 2 (n=21) and 3 (n=19). Median time from irAE onset to radiotherapy was 8.1 months. Most patients received SBRT (n=20) or hypofractionated radiotherapy (n=18). In total, 25 patients (61%) developed ≥ grade 2 RP at a median of 4 months from radiotherapy and 11 months from onset of irAEs. Three months from RP onset, 16 of 24 (67%) evaluable patients had persistent symptoms. Among patients with prior ICI pneumonitis (n=6), 5 patients (83%) developed ≥ grade 2 RP (grade 2, n=3; grade ≥3, n=2). The mean lung radiation dose (MLD) predicted for RP (OR: 1.60, p = 0.00002). The relationship between MLD and RP was strong (AUC: 0.85) and showed an exaggerated dose-response. Among patients with an MLD > 5Gy (n=26), 21 patients (81%) developed ≥ grade 2 RP.
This is the first study assessing the toxicity of radiotherapy among patients with prior irAEs from ICIs. Patients with prior irAEs were found to be at very high-risk for clinically significant and persistent RP from thoracic radiotherapy. Careful consideration should be given to the possibility of an increased risk of RP, and close monitoring is recommended, in these patients.