Cancer Research and Treatment

Original Article

Lung and Thoracic cancer

Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study: Naoya Nishioka, Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama; Cancer Res Treat. 2025;57(2):412-421. Published online October 25, 2024; DOI: https://doi.org/10.4143/crt.2024.748

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Purpose
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

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TTF-1 Negativity Predicts Poor Outcomes in Advanced Non-Squamous NSCLC Also in the Immunotherapy Era: A Multicenter Cohort Study and Meta-Analysis
Leonardo Brunetti, Valentina Santo, Alessandro Galletti, Alain Gelibter, Antonio Lugini, Gian Paolo Spinelli, Daniele Santini, Alessio Cortellini, Alessia Vendittelli, Giuseppina Rita Di Fazio, Fabrizio Citarella, Giulia La Cava, Emanuele Claudio Mingo, M
Cancers.2025; 17(13): 2188. CrossRef

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