Outcomes Following Radiotherapy for Oligoprogressive NSCLC on Immune Checkpoint Inhibitors: A Real-World, Multinational Experience

<b>Purpose</b>: We conducted the largest multinational review to date evaluating outcomes following radiotherapy for non-small cell lung carcinoma (NSCLC) patients with oligoprogressive disease (OPD) on immune checkpoint inhibitors (ICIs). <b>Methods</b>: Patients with NSCLC irradiated to ≤5 progressive lesions while receiving ICIs between 2010 and 2023 were identified. We evaluated predictors of local control (LC), progression-free survival (PFS), and overall survival (OS). Patient demographics, disease characteristics, and survival were analyzed using the Wilcoxon test, Kaplan-Meier methods, and uni-/multivariate Cox models. <b>Results</b>: Out of 1178 treated patients, 103 eligible ones were included. The median OPD lesion was 1; the most common site was the lung (n = 33). The median LC of irradiated OPD lesions was not reached. Median PFS and OS were 6.90 (5.75-12.91) and 23.46 (17.54-37.16) months, respectively. Patient demographics, tumor pathological factors, number of OPD lesions, cumulative tumor volume, radiation modality, and OPD response to prior ICIs before radiation were not associated with these three outcomes. However, LC was associated with intermediate/high radiation doses (<i>p</i> = 0.005) and local response to radiation (<i>p</i> = 0.007). Improved PFS was associated with visceral OPD sites following radiation (<i>p</i> = 0.01). A favorable OS was associated with intermediate/high radiation doses (<i>p</i> = 0.01), local response to radiation (<i>p</i> = 0.006), and duration of last ICI before OPD (<i>p</i> = 0.03). <b>Conclusions</b>: Promising outcomes were observed with ICI and radiation for visceral OPD at intermediate/high doses. Prolonged ICI use before OPD and local response to radiotherapy improved survival. These data can contribute towards guidance of multidisciplinary clinical decision-making for managing OPD in NSCLC patients receiving ICIs.