TTF-1 negativity in synchronous M1b/M1c wildtype lung adenocarcinoma brain metastases predicts worse survival with increased risk of intracranial progression.

IF 3.2 2区医学 Q2 CLINICAL NEUROLOGY

Journal of Neuro-Oncology Pub Date : 2024-12-04 DOI:10.1007/s11060-024-04885-y

David Wasilewski, Tommaso Araceli, Philip Bischoff, Anton Früh, Rober Ates, Selin Murad, Niklas Jung, Jan Bukatz, Majd Samman, Katharina Faust, Julia Jünger, Martin Witzenrath, David Horst, Atik Baborie, Arend Koch, David Capper, Frank L Heppner, Helena Radbruch, Markus J Riemenschneider, Nils Ole Schmidt, Peter Vajkoczy, Martin Proescholdt, Julia Onken, Nikolaj Frost

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引用次数: 0

Abstract

Background: 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.

Material and methods: 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.

Results: 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 < 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.

Conclusion: 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.

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来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.