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

Sep 30, 2026

Purpose: Conducted the largest multinational review assessing outcomes after radiotherapy in non-small cell lung carcinoma (NSCLC) patients with oligoprogressive disease (OPD) receiving immune checkpoint inhibitors (ICIs). Methods: Identified patients treated with ≤5 progressive lesions between 2010 and 2023 and evaluated predictors of local control, progression-free survival, and overall survival using Wilcoxon testing, Kaplan–Meier analysis, and uni-/multivariate Cox models. Results: 103 eligible patients; median PFS 6.90 months and OS 23.46 months. Radiation dose and local response correlated with local control and survival; favorable OS also related to duration of prior ICI and improved PFS to visceral OPD sites.

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CategoryHealthcare

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Article Outcomes Following Radiotherapy for Oligoprogressive NSCLC on Immune Checkpoint Inhibitors: A Real-World, Multinational Experience Umair Mahmood 1,2,*, Eleni Josephides 1, Nicholas Coupe 2, Daniel Smith 1, Shahreen Ahmad 1, Omar Al-Salihi 1, Sze M. Mak 3, Meenali Chitnis 2, Alexandros Georgiou 1, Daniel Ajzensztejn 2, Eleni Karapanagiotou 1, Geoff S. Higgins 2, Niki Panakis 2, Jonathan D. Schoenfeld 4 and Michael Skwarski 1, * Academic Editor: Gabriele Multhoff Received: 28 November 2025 Revised: 22 December 2025 Accepted: 23 December 2025 Published: 25 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Oncology, Guy’s and St. Thomas’ NHS Foundation Trust, London SE1 9RT, UK 2 Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK 3 Department of Radiology, Guy’s and St. Thomas’ NHS Foundation Trust, London SE1 9RT, UK 4 Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA * [Correspondence: umair.mahmood1@nhs.net](Correspondence: umair.mahmood1@nhs.net) (U.M.); [michael.skwarski@nhs.net](michael.skwarski@nhs.net) (M.S.); Tel.: +44-020-7188-7188 (U.M. & M.S.) Simple Summary 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. Abstract 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

FAQs

What population was studied in this review?

NSCLC patients with oligoprogressive disease while receiving immune checkpoint inhibitors, irradiated to no more than five progressive lesions.

Which outcomes were assessed?

The study evaluated local control, progression-free survival, and overall survival as primary endpoints.

What factors were associated with better survival outcomes?

Higher/intermediate radiation doses, local response to radiotherapy, and—depending on the endpoint—visceral OPD sites and longer duration of the last ICI before OPD were associated with improved outcomes.

Sep 30, 2026

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