{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:58:16Z","timestamp":1781161096564,"version":"3.54.1"},"reference-count":121,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Advances in systemic therapy have improved outcomes for metastatic non\u2013small cell lung cancer (NSCLC), yet resistance and progression remain nearly universal. Local therapies such as radiotherapy, surgery, and image-guided ablation can extend disease control in selected patients, but existing classifications\u2014including dynamic models of oligometastatic disease\u2014assign a single state per patient and do not capture lesion-level heterogeneity. We introduce the concept of\n                      <jats:italic toggle=\"yes\">metastatic trajectories<\/jats:italic>\n                      \u2014the spatiotemporal dynamics of response and progression across lesions, organs, and patients\u2014as a framework to characterize intrapatient heterogeneity and inform adaptive treatment strategies. Dimensions of metastatic trajectories include the magnitude and homogeneity of response, mechanisms of resistance, organotropism, and the pattern, site, extent, and pace of progression. This framework shifts the focus from overall disease states to individual lesion behavior over time, enabling\n                      <jats:italic toggle=\"yes\">reactive<\/jats:italic>\n                      strategies based on observed trajectories and\n                      <jats:italic toggle=\"yes\">anticipatory<\/jats:italic>\n                      strategies based on predicted ones. We review the biological foundations of intrapatient heterogeneity\u2014including genomic diversification, nongenetic plasticity, and tumor-microenvironmental adaptation\u2014that drive divergent lesion evolution and treatment response. Emerging biomarkers such as circulating tumor DNA and radiomic signatures, together with integrative genomic and functional imaging approaches, may allow tracking and prediction of trajectory evolution. Standardized reporting parameters are proposed to ensure consistent documentation and facilitate validation across studies. Integrating trajectory-based assessment into clinical practice could refine patient selection for local and systemic therapy, enable biology-informed adaptation of treatment timing and intensity, and provide a foundation for next-generation clinical trials aimed at precision management of metastatic NSCLC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01958","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:00:21Z","timestamp":1778011221000},"page":"1540-1552","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Metastatic Trajectories in Non\u2013Small Cell Lung Cancer Guide Local and Systemic Therapies"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-3551","authenticated-orcid":false,"given":"Jonas","family":"Willmann","sequence":"first","affiliation":[{"name":"Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6119-0889","authenticated-orcid":true,"given":"Edward Christopher","family":"Dee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3521-2535","authenticated-orcid":true,"given":"Lizza E.L.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, GROW-Research Institute for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-202X","authenticated-orcid":true,"given":"Nikolaos M.","family":"Dimitriou","sequence":"additional","affiliation":[{"name":"Halvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4686-9169","authenticated-orcid":true,"given":"Mandy","family":"Jongbloed","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, GROW-Research Institute for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-1416","authenticated-orcid":true,"given":"Adam J.","family":"Schoenfeld","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9061","authenticated-orcid":true,"given":"Alexander","family":"Drilon","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-1372","authenticated-orcid":true,"given":"Karuna","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-472X","authenticated-orcid":true,"given":"Y. 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