{"doi":"10.1200/jco.23.02668","title":"Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From <i>EGFR</i> and <i>ALK</i> Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)","abstract":"PURPOSE Newer-generation tyrosine kinase inhibitors (TKIs) for non–small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR ) mutations and anaplastic lymphoma kinase ( ALK ) 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. MATERIALS AND METHODS Data on TKI-naïve 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. RESULTS 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 ≥1 cm ( P &lt; .001) and neurologic symptoms ( P &lt; .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v 40 months, respectively; P = .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]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P &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 ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival. CONCLUSION 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 - and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.","journal":"Journal of Clinical Oncology","year":2024,"id":418563,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":976779,"name":"Emily Miao","orcid":"0000-0001-8848-2830","position":1,"is_corresponding":false},{"id":802893,"name":"Lillian A. 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Thomas","orcid":"0000-0003-4931-4716","position":19,"is_corresponding":false},{"id":259414,"name":"Steve Braunstein","orcid":"0000-0002-9841-9357","position":20,"is_corresponding":false},{"id":7950,"name":"Brian D. Kavanagh","orcid":"0000-0001-5579-1725","position":21,"is_corresponding":false},{"id":230277,"name":"D. Ross Camidge","orcid":"0000-0003-3430-3213","position":22,"is_corresponding":false},{"id":225613,"name":"Chad G. Rusthoven","orcid":"0000-0002-6978-2077","position":23,"is_corresponding":false},{"id":764251,"name":"Luke Pike","orcid":"0000-0001-9622-7442","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T01:57:09.067930Z","pmid":"39047224","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}