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

## TL;DR

This study examines the outcomes of radiotherapy for lung cancer patients whose disease slightly progresses while on immune therapy, aiming to guide better treatment choices.

## Contribution

The study provides the largest multinational analysis of radiotherapy outcomes for oligoprogressive NSCLC on immune checkpoint inhibitors.

## Key findings

- Radiotherapy at intermediate/high doses improved local control and survival in patients with visceral oligoprogressive lesions.
- Prolonged use of immune checkpoint inhibitors before progression and a positive response to radiotherapy were linked to better survival outcomes.
- The number of lesions, tumor volume, and prior ICI response were not associated with outcomes, suggesting other factors drive treatment success.

## Abstract

NSCLC patients with oligoprogression on immune checkpoint inhibitors (ICIs) represent an emerging clinical population, but there is limited data to guide clinical decision-making as to the optimal treatment strategy. We aimed to identify clinical and pathological factors in NSCLC that improve stratification of patients most likely to benefit from radiotherapy for oligoprogressive disease with or without ICIs. Because ICIs can offer durable responses with fewer toxicities than other systemic therapies, determining which patients can safely remain on ICIs is clinically valuable. We aimed to identify which patients benefit meaningfully from radiation and which are unlikely to benefit and may require alternative systemic strategies. This study has the potential to refine patient selection, reduce unnecessary radiation exposure, and improve treatment personalization. In addition to informing clinical practice, our data can also guide future trials evaluating radiation for oligoprogressive NSCLC as an alternative to changing systemic therapy or pursuing more invasive local surgery.

Purpose: 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). Methods: 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. Results: 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 (p = 0.005) and local response to radiation (p = 0.007). Improved PFS was associated with visceral OPD sites following radiation (p = 0.01). A favorable OS was associated with intermediate/high radiation doses (p = 0.01), local response to radiation (p = 0.006), and duration of last ICI before OPD (p = 0.03). Conclusions: 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.