{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:16:55Z","timestamp":1784121415604,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guy\u2019s Cancer Academy and Friends of Guy\u2019s and St. Thomas Hospital Charity","award":["22\/01R"],"award-info":[{"award-number":["22\/01R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u22645 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\u201312.91) and 23.46 (17.54\u201337.16) 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.<\/jats:p>","DOI":"10.3390\/cancers18010071","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:07:58Z","timestamp":1766714878000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Outcomes Following Radiotherapy for Oligoprogressive NSCLC on Immune Checkpoint Inhibitors: A Real-World, Multinational Experience"],"prefix":"10.3390","volume":"18","author":[{"given":"Umair","family":"Mahmood","sequence":"first","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"},{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Josephides","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Coupe","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6330-3936","authenticated-orcid":false,"given":"Daniel","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahreen","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Al-Salihi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze M.","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Radiology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5414-7907","authenticated-orcid":false,"given":"Meenali","family":"Chitnis","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-9251","authenticated-orcid":false,"given":"Alexandros","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ajzensztejn","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5873-6964","authenticated-orcid":false,"given":"Eleni","family":"Karapanagiotou","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff S.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Panakis","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Schoenfeld","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0395-4881","authenticated-orcid":false,"given":"Michael","family":"Skwarski","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e192535","DOI":"10.1001\/jamanetworkopen.2019.2535","article-title":"Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs","volume":"2","author":"Haslam","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ccell.2020.03.017","article-title":"Acquired Resistance to Immune Checkpoint Inhibitors","volume":"37","author":"Schoenfeld","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1200\/JCO.20.00818","article-title":"Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial","volume":"38","author":"Palma","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1016\/S0140-6736(18)32487-5","article-title":"Stereotactic Ablative Radiotherapy versus Standard of Care Palliative Treatment in Patients with Oligometastatic Cancers (SABR-COMET): A Randomised, Phase 2, Open-Label Trial","volume":"393","author":"Palma","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e173501","DOI":"10.1001\/jamaoncol.2017.3501","article-title":"Consolidative Radiotherapy for Limited Metastatic Non\u2013Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial","volume":"4","author":"Iyengar","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1200\/JCO.19.00201","article-title":"Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients with Oligometastatic Non\u2013Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study","volume":"37","author":"Gomez","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ijrobp.2020.02.019","article-title":"Oligometastasis: Past, Present, Future","volume":"108","author":"Gutiontov","year":"2020","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.clon.2019.05.015","article-title":"The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively?","volume":"31","author":"Patel","year":"2019","journal-title":"Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104676","DOI":"10.1016\/j.critrevonc.2025.104676","article-title":"Consolidative Radiotherapy in Oligometastatic and Oligoprogressive NSCLC: A Systematic Review","volume":"210","author":"Hasan","year":"2025","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal Toxic Effects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1200\/JCO.18.00149","article-title":"Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer with PD-L1 Tumor Proportion Score of 50% or Greater","volume":"37","author":"Reck","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus Docetaxel in Advanced Nonsquamous Non\u2013Small-Cell Lung Cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mahmood, U., Josephides, E., Chitnis, M., Skwarski, M., Gennatas, S., Ghosh, S., Spicer, J., Karapanagiotou, E., Ahmad, T., and Forster, M. (2025). Predictors and Outcomes of Non-Small Cell Lung Carcinoma Patients Following Severe Immune Checkpoint Inhibitor Toxicity: A Real-World UK Multi-Centre Study. Cancers, 17.","DOI":"10.3390\/cancers17172819"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1056\/NEJMc1716612","article-title":"Hazards of Hazard Ratios\u2014Deviations from Model Assumptions in Immunotherapy","volume":"378","author":"Alexander","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ijrobp.2022.05.008","article-title":"Retrospective Review of Outcomes After Radiation Therapy for Oligoprogressive Disease on Immune Checkpoint Blockade","volume":"114","author":"Mahmood","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.radonc.2020.04.003","article-title":"Defining Oligometastatic Disease from a Radiation Oncology Perspective: An ESTRO-ASTRO Consensus Document","volume":"148","author":"Lievens","year":"2020","journal-title":"Radiother. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s40425-019-0672-3","article-title":"Patterns of Failure after Immunotherapy with Checkpoint Inhibitors Predict Durable Progression-Free Survival after Local Therapy for Metastatic Melanoma","volume":"7","author":"Klemen","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0140-6736(23)01857-3","article-title":"Consolidative Use of Radiotherapy to Block (CURB) Oligoprogression\u2014Randomised Study of Standard-of-Care Systemic Therapy with or without Stereotactic Body Radiotherapy in Patients with Oligoprogressive Cancers of the Breast and Lung","volume":"403","author":"Tsai","year":"2024","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1001\/jamaoncol.2019.1449","article-title":"Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non\u2013Small Cell Lung Cancer: A Phase 2 Trial","volume":"5","author":"Bauml","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.21037\/jtd.2019.12.23","article-title":"Outcomes from Salvage Chemotherapy or Pembrolizumab beyond Progression with or without Local Ablative Therapies for Advanced Non-Small Cell Lung Cancers with PD-L1 \u226550% Who Progress on First-Line Immunotherapy: Real-World Data from a European Cohort","volume":"11","author":"Metro","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jtho.2018.03.008","article-title":"Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients with Advanced Non\u2013Small Cell Lung Cancer","volume":"13","author":"Gettinger","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.prro.2023.04.004","article-title":"Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO\/ESTRO Clinical Practice Guideline","volume":"13","author":"Iyengar","year":"2023","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/COC.0b013e3181ec63ae","article-title":"Stereotactic Radiotherapy Reduces Treatment Cost While Improving Overall Survival and Local Control over Standard Fractionated Radiation Therapy for Medically Inoperable Non-Small-Cell Lung Cancer","volume":"34","author":"Lanni","year":"2011","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1634\/theoncologist.2017-0384","article-title":"Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab","volume":"23","author":"Toi","year":"2018","journal-title":"Oncologist"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-Related Adverse Events Associated with Immune Checkpoint Blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T Cells in Health and Disease","volume":"8","author":"Sun","year":"2023","journal-title":"Sig Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e005509","DOI":"10.1136\/jitc-2022-005509","article-title":"Clonal Expansion of Resident Memory T Cells in Peripheral Blood of Patients with Non-Small Cell Lung Cancer during Immune Checkpoint Inhibitor Treatment","volume":"11","author":"Kim","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106214","DOI":"10.1016\/j.intimp.2020.106214","article-title":"Predictive Effect of PD-L1 Expression for Immune Checkpoint Inhibitor (PD-1\/PD-L1 Inhibitors) Treatment for Non-Small Cell Lung Cancer: A Meta-Analysis","volume":"80","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/25785826.2021.1997268","article-title":"Radiotherapy Driven Immunomodulation of the Tumor Microenvironment and Its Impact on Clinical Outcomes: A Promising New Treatment Paradigm","volume":"45","author":"Mahmood","year":"2022","journal-title":"Immunol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S323","DOI":"10.1016\/j.jtho.2024.09.580","article-title":"P3.06D.05 Stratifying Risk in Oligoprogressive EGFR-Mutated Non-Small Cell Lung Cancer: The Role of ctDNA","volume":"19","author":"Arrieta","year":"2024","journal-title":"J. Thorac. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/71\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:17:47Z","timestamp":1766715467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,25]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cancers18010071"],"URL":"https:\/\/doi.org\/10.3390\/cancers18010071","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,25]]}}}