{"doi":"10.1007/s11060-024-04885-y","title":"TTF-1 negativity in synchronous M1b/M1c wildtype lung adenocarcinoma brain metastases predicts worse survival with increased risk of intracranial progression","abstract":"<jats:title>Abstract</jats:title>\n          <jats:sec>\n            <jats:title>Background</jats:title>\n            <jats:p>Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Material and methods</jats:title>\n            <jats:p>In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan–Meier estimates and Cox proportional hazards regression.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results</jats:title>\n            <jats:p>Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38–48%] compared to 32% [95% CI 29–35%] in TTF-1 positive (TTF-1 +) patients (p &lt; 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18–31 mL]) vs. 15 mL [95% CI 12–17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45–70 mL]) vs. 84 mL [95% CI 73–94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion</jats:title>\n            <jats:p>In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype.</jats:p>\n          </jats:sec>","journal":"Journal of Neuro-Oncology","year":2025,"id":609140,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1565507,"name":"Tommaso Araceli","orcid":null,"position":1,"is_corresponding":false},{"id":1304114,"name":"Philip Bischoff","orcid":"0000-0002-4442-7116","position":2,"is_corresponding":false},{"id":1565508,"name":"Anton Früh","orcid":null,"position":3,"is_corresponding":false},{"id":1565509,"name":"Rober Ates","orcid":null,"position":4,"is_corresponding":false},{"id":1565510,"name":"Selin Murad","orcid":null,"position":5,"is_corresponding":false},{"id":1565511,"name":"Niklas Jung","orcid":null,"position":6,"is_corresponding":false},{"id":1565512,"name":"Jan Bukatz","orcid":null,"position":7,"is_corresponding":false},{"id":1565513,"name":"Majd Samman","orcid":null,"position":8,"is_corresponding":false},{"id":863254,"name":"Katharina Faust","orcid":"0000-0001-9969-0141","position":9,"is_corresponding":false},{"id":1565514,"name":"Julia Jünger","orcid":null,"position":10,"is_corresponding":false},{"id":57974,"name":"Martin Witzenrath","orcid":"0000-0002-9787-5633","position":11,"is_corresponding":false},{"id":57964,"name":"David Horst","orcid":"0000-0003-4755-5743","position":12,"is_corresponding":false},{"id":1565515,"name":"Atik Baborie","orcid":null,"position":13,"is_corresponding":false},{"id":695865,"name":"Arend Koch","orcid":null,"position":14,"is_corresponding":false},{"id":660735,"name":"David Capper","orcid":"0000-0003-1945-497X","position":15,"is_corresponding":false},{"id":57967,"name":"Frank L. Heppner","orcid":"0000-0001-9816-8917","position":16,"is_corresponding":false},{"id":57980,"name":"Helena Radbruch","orcid":"0000-0001-6941-3397","position":17,"is_corresponding":false},{"id":27625,"name":"Markus J. Riemenschneider","orcid":"0000-0001-7658-1022","position":18,"is_corresponding":false},{"id":1565516,"name":"Nils Ole Schmidt","orcid":null,"position":19,"is_corresponding":false},{"id":317381,"name":"Peter Vajkoczy","orcid":"0000-0003-4350-392X","position":20,"is_corresponding":false},{"id":133233,"name":"Martin Proescholdt","orcid":null,"position":21,"is_corresponding":false},{"id":1010911,"name":"Julia Onken","orcid":"0000-0002-2859-4395","position":22,"is_corresponding":false},{"id":98579,"name":"Nikolaj Frost","orcid":"0000-0001-7452-7129","position":23,"is_corresponding":false},{"id":1565506,"name":"David Wasilewski","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"TTF-1 negativity in synchronous M1b/M1c wildtype lung adenocarcinoma brain metastases predicts worse survival with increased risk of intracranial progression","abstract":"<jats:title>Abstract</jats:title>\n          <jats:sec>\n            <jats:title>Background</jats:title>\n            <jats:p>Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Material and methods</jats:title>\n            <jats:p>In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan–Meier estimates and Cox proportional hazards regression.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results</jats:title>\n            <jats:p>Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38–48%] compared to 32% [95% CI 29–35%] in TTF-1 positive (TTF-1 +) patients (p &lt; 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18–31 mL]) vs. 15 mL [95% CI 12–17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45–70 mL]) vs. 84 mL [95% CI 73–94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion</jats:title>\n            <jats:p>In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39630375","pmcid":"PMC11729080","openalex_id":"https://openalex.org/W4405013288","authors":[],"funders":[{"funder_name":"Charité - Universitätsmedizin Berlin","grant_id":"","title":null}],"total_grants":1,"fwci":1.7059,"citation_percentile":0.85768934,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s11060-024-04885-y.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s11060-024-04885-y.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s11060-024-04885-y/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s11060-024-04885-y","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39630375","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11729080","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11729080/pdf/11060_2024_Article_4885.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11729080","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11729080?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Brain Metastases and Treatment","Lung Cancer Treatments and Mutations","Lung Cancer Research Studies","Humans","Brain Neoplasms","Male","Female","Middle Aged","Thyroid Nuclear Factor 1","Lung Neoplasms","Adenocarcinoma of Lung","Retrospective Studies","Aged","Prognosis","Disease Progression","Biomarkers, Tumor","Adult","Survival Rate","Follow-Up Studies","Aged, 80 and over","DNA-Binding Proteins","Transcription Factors"],"mesh_terms":["Thyroid Nuclear Factor 1","Adenocarcinoma of Lung","Adult","Aged","Aged, 80 and over","Brain Neoplasms","DNA-Binding Proteins","Female","Follow-Up Studies","Humans","Lung Neoplasms","Male","Middle Aged","Prognosis","Retrospective Studies","Transcription Factors","Biomarkers, Tumor","Survival Rate","Disease Progression"],"keywords":["Medicine","Internal medicine","Proportional hazards model","Hazard ratio","Brain metastasis","Oncology","Adenocarcinoma","Gastroenterology","Lung cancer","Retrospective cohort study","Cancer","Metastasis","Confidence interval","Survival","Ki67","Tumor Volume","Ttf-1","Edema Volume","Luad"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T03:45:20.603154Z","pmid":null,"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":[]}