Cancer Res Treat.  2025 Apr;57(2):412-421. 10.4143/crt.2024.748.

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

• Nishioka N
• Hata T
• Yamada T
• Goto Y
• Amano A
• Negi Y
• Watanabe S
• Furuya N
• Oba T
• Ikoma T
• Nakao A
• Tanimura K
• Taniguchi H
• Yoshimura A
• Fukui T
• Murata D
• Kaira K
• Shiotsu S
• Hibino M
• Okada A
• Chihara Y
• Kawachi H
• Kijima T
• Takayama K

• KMID: 2566860
• DOI: http://doi.org/10.4143/crt.2024.748

Abstract

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.

Keyword

Thyroid transcription factor 1; PD-L1; Non-small-cell lung carcinoma; Chemoimmunotherapy; Chemotherapy

Figure

• 

  Fig. 1. Comparison of treatment efficacy between thyroid transcription factor-1 (TTF-1)–positive and negative groups in the chemotherapy and chemoimmunotherapy cohorts. Kaplan-Meier curves for progression-free survival (PFS) (A) and overall survival (OS) (B) in the chemotherapy cohorts. Kaplan-Meier curves for PFS (C) and OS (D) in the chemoimmunotherapy cohort. CI, confidence interval.

• 

  Fig. 2. Comparison of overall survival (OS) between pemetrexed (PEM)-based and non-PEM–based regimens within the chemotherapy and chemoimmunotherapy cohorts stratified by thyroid transcription factor-1 (TTF-1) expression status. We compared the OS between the PEM-based and non-PEM–based regimen groups in the chemotherapy and chemotherapy cohorts stratified by TTF-1 expression status. Kaplan-Meier curves are shown for the chemotherapy (A) and chemoimmunotherapy (B) groups in the TTF-1–positive population and for the chemotherapy (C) and chemoimmunotherapy (D) groups in the TTF-1–negative population. CI, confidence interval.

Reference

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