ArticleInternational journal of clinical oncology2026
Predictive value of TTF-1 expression for stratifying outcomes between dual ICI and chemoimmunotherapy in patients with PD-L1-negative NSCLC.
Article in International journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThyroid transcription factor-1 (TTF-1) has emerged as a novel predictive biomarker associated with the prognosis and treatment response of non-squamous non-small-cell lung cancer (NSCLC) to cytotoxic chemotherapy. This study evaluated the clinical significance of TTF-1 expression in advanced NSCLC with programmed death-ligand 1 (PD-L1) < 1%, with a specific focus on its utility in stratifying treatment outcomes between dual immune checkpoint inhibitor (IO-IO) therapy and chemoimmunotherapy.
methodsWe conducted a multicenter retrospective study across 22 Japanese institutions, evaluating 194 patients with advanced or recurrent non-squamous NSCLC and PD-L1 < 1% treated with IO-IO therapy or chemoimmunotherapy between 2019 and 2022. Survival outcomes were analyzed using multivariable Cox regression.
resultsTTF-1-positive patients had significantly longer progression-free survival (PFS) and overall survival (OS) than TTF-1-negative patients [adjusted hazard ratio (HR) for PFS: 0.65, p = 0.009; adjusted HR for OS: 0.69, p = 0.04]. Among TTF-1-positive patients, no significant difference in survival was observed between IO-IO therapy and chemoimmunotherapy. By contrast, TTF-1-negative patients experienced significantly improved outcomes with chemoimmunotherapy than with IO-IO therapy (adjusted HR for PFS: 0.37, p = 0.01; adjusted HR for OS: 0.39, p = 0.02).
conclusionTTF-1 expression may serve as a prognostic and potentially predictive biomarker in PD-L1-negative NSCLC patients. TTF-1-negative patients appeared to derive greater benefit from the addition of chemotherapy. These findings suggest that TTF-1 expression may have potential utility in guiding treatment selection and warrant prospective validation.
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