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In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)\u2014complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.<\/jats:p>","DOI":"10.3390\/ijms25084533","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"4533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4778-4271","authenticated-orcid":false,"given":"Juan","family":"Zafra","sequence":"first","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Department of Radiation Oncology, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"},{"name":"Faculty of Medicine, University of Malaga (UMA), 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-8099","authenticated-orcid":false,"given":"Juan Luis","family":"Onieva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Malaga (UMA), 29071 M\u00e1laga, Spain"},{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-4711","authenticated-orcid":false,"given":"Javier","family":"Oliver","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Garrido-Barros","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Malaga (UMA), 29071 M\u00e1laga, Spain"},{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gonz\u00e1lez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Malaga (UMA), 29071 M\u00e1laga, Spain"},{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mart\u00ednez-G\u00e1lvez","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Ord\u00f3\u00f1ez-Marmolejo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-0800","authenticated-orcid":false,"given":"Elisabeth","family":"P\u00e9rez-Ruiz","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-9132","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Ben\u00edtez","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rueda-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-6502","authenticated-orcid":false,"given":"Isabel","family":"Barrag\u00e1n","sequence":"additional","affiliation":[{"name":"Group of Translational Research in Cancer Immunotherapy (CIMO2), Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria Hospitals, Institute of Biomedical Research in Malaga (IBIMA), 29010 M\u00e1laga, Spain"},{"name":"Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, 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