{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:25:55Z","timestamp":1791822355643,"version":"4.3.4"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,10,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Newer-generation tyrosine kinase inhibitors (TKIs) for non\u2013small cell lung cancer (NSCLC) with epidermal growth factor receptor (\n                      <jats:italic>EGFR<\/jats:italic>\n                      ) mutations and anaplastic lymphoma kinase (\n                      <jats:italic>ALK<\/jats:italic>\n                      ) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>Data on TKI-na\u00efve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine &amp; Gray and Cox proportional hazards models for clinically relevant factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM \u22651 cm (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001) and neurologic symptoms (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41\n                      <jats:italic>v<\/jats:italic>\n                      40 months, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96];\n                      <jats:italic>P<\/jats:italic>\n                      = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55];\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM \u22651 cm in diameter for time-to-CNS progression and CNS progression-free survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR\n                      <jats:italic>-<\/jats:italic>\n                      and ALK-driven NSCLC. Patients with larger BM (\u22651 cm) may benefit the most from up-front SRS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.23.02668","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T16:03:44Z","timestamp":1721837024000},"page":"3606-3617","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":57,"title":["Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From\n                    <i>EGFR<\/i>\n                    and\n                    <i>ALK<\/i>\n                    Oncogene\u2013Driven Non\u2013Small Cell Lung Cancer (TURBO-NSCLC)"],"prefix":"10.1200","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9622-7442","authenticated-orcid":false,"given":"Luke R.G.","family":"Pike","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New 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