Dosimetric Risk Factors for Radiation Pneumonitis in Patients with Prior Receipt of Immune Checkpoint Inhibitors: A Retrospective Study

Abstract

<h3>Purpose/Objective(s)</h3> Dosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far. <h3>Materials/Methods</h3> All included patients underwent thoracic irradiation, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis. <h3>Results</h3> Median follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD, V20=5.2% and MDL=4.0Gy would predict for a 50% risk of ≥ grade 1 pneumonia, and V20=19.3% would predict for a 50% risk for grade 2 pneumonia. <h3>Conclusion</h3> This is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.