{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:56:16Z","timestamp":1792184176203,"version":"4.4.0"},"reference-count":33,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Cancer Institute at the National Institutes of Health through the Cancer Cen-ter Core","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"Clinical and Translational Science Award","award":["UL1 RR024148"],"award-info":[{"award-number":["UL1 RR024148"]}]},{"name":"Bristol-Myers Squibb and MD Anderson Cancer Center Alliance","award":["CA209-925"],"award-info":[{"award-number":["CA209-925"]}]},{"name":"Texas 4000 Distinguished Professorship at the MD Anderson Cancer Center and the Joan and Herb Kelleher Charitable Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,11]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named \u201cI-SABR-SELECT\u201d) based on clinical and radiomic factors to address which patients should receive additional immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The discovery\/validation cohorts were from the I-SABR trial, with external validation from the single-arm STARS trial. Individual treatment effect scores, estimating the benefit of adding immunotherapy, were derived from radiomic and clinical predictors using counterfactual reasoning. Dimensionality reduction was applied to mitigate overfitting and enhance model robustness. We also evaluated the average treatment effect between subgroups of patients who were treated following versus against the model\u2019s recommendation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The model recommended that 49% (69\/141) patients enrolled in the I-SABR trial switch treatments (65% (49\/75) in the SABR arm and 30% (20\/66) in the I-SABR arm). Patients treated by the model\u2019s recommendation had higher EFS, with HRs of 0.06 (in the I-SABR arm, p&lt;0.001) and 0.26 (in the SABR alone arm, p=0.0042) from the I-SABR trial population, and 0.38 (p=0.031) for the STARS trial. Following model stratification, among patients recommended for SABR+immunotherapy, the restricted mean survival time for EFS is prolonged by 1.43 years compared to those who received SABR alone. The absolute risk reduction of the added immunotherapy effect was over twofold greater than that observed in the I-SABR trial without selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combining clinical and radiomic parameters, I-SABR-SELECT uses causal reasoning to individualize treatment selection for patients with early-stage inoperable NSCLC. If validated, it could serve as a foundation for a treatment-focused digital twin by integrating real-time adaptive decision-making.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Code:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/WuLabMDA\/ISABR-SELECT\">https:\/\/github.com\/WuLabMDA\/ISABR-SELECT<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013074","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:30:32Z","timestamp":1759732232000},"page":"e013074","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Causal AI-based clinical and radiomic analysis for optimizing patient selection in combined immunotherapy and SABR in early-stage NSCLC: a secondary analysis of the phase II I-SABR trial"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03110978","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03924869","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03833154","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04214262","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Maliazurina B","family":"Saad","sequence":"first","affiliation":[{"name":"Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Showkatian","sequence":"additional","affiliation":[{"name":"Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Thoracic 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