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Research Article|Articles in Press, 100494

Thyroid transcription factor 1 expression related to clinical outcomes of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma: a prospective observational study1

Open AccessPublished:March 07, 2023DOI:https://doi.org/10.1016/j.jtocrr.2023.100494
Thyroid transcription factor 1 expression related to clinical outcomes of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma: a prospective observational study1
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      Abstract

      Introduction

      Lung adenocarcinoma with negative thyroid transcription factor 1 (TTF-1) expression is believed to be a poor prognostic factor for certain systemic treatments. However, the impact of TTF-1 expression on combined chemoimmunotherapy remains unclear. We aimed to investigate the relationship between tumor TTF-1 expression and the efficacy of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma.

      Methods

      This multicenter prospective observational study included 58 patients with advanced lung adenocarcinoma treated with combined chemoimmunotherapy across 10 institutions in Japan. The expression of TTF-1 in pretreatment tumors was determined using immunohistochemistry.

      Results

      The objective response rate of combined chemoimmunotherapy was significantly higher in TTF-1–positive groups than in TTF-1–negative groups (p = 0.02). The median progression-free survival (PFS) and overall survival were significantly longer in TTF-1–positive groups than in TTF-1–negative groups (10.9 vs. 5.0 months; p = 0.01). Multivariate analysis revealed that TTF-1 expression was an independent favorable prognostic factor for PFS. Moreover, TTF-1 expression in patients with lung adenocarcinoma is significantly associated with programmed death ligand 1 (PD-L1) expression (p = 0.003). The TTF-1–positive group with PD-L1 tumor proportion score ≥50% had a significantly longer PFS than other groups (p = 0.02).

      Conclusions

      TTF-1 positivity is associated with better clinical outcomes in patients with advanced lung adenocarcinoma treated with first-line combined chemoimmunotherapy.

      Keywords

      1Abbreviations:

      (TTF-1) (thyroid transcription factor 1), (PFS) (progression-free survival), (PD-L1) (programmed death ligand 1), (NSCLC) (non-small cell lung cancer), (ICI) (immune checkpoint inhibitor), (TPS) (tumor-proportion score), (OS) (overall survival), (ORR) (objective response rate), (HR) (hazard ratios), (CI) (confidence interval), (ECOG-PS) (Eastern Cooperative Oncology Group Performance Status), (EGFR) (epidermal growth factor receptor), (VEGF) (vascular endothelial growth factor)

      Article info

      Publication history

      Accepted: March 2, 2023
      Received in revised form: February 28, 2023
      Received: December 16, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Funding: This work was supported by research grants from the Medical Research Continuous Grants of the Takeda Science Foundation and the Princess Takamatsu Cancer Research Fund (both to Tadaaki Yamada)

      Declaration of interest: Dr. Yamada reports receiving research grants from Pfizer Inc., Ono Pharmaceutical, Janssen Pharmaceutical, AstraZeneca PLC, and Takeda Pharmaceutical and personal fees from Eli Lilly. Dr. Kim reports receiving research grants from Chugai-Roche Co., AstraZeneca PLC, and Eli Lilly Co. and personal fees from AstraZeneca Co. and Chugai-Roche Co. Dr. Takayama reports receiving research grants from Chugai-Roche Co. and Ono Pharmaceutical Co. and personal fees from AstraZeneca Co., Chugai-Roche Co., MSD-Merck Co., Eli Lilly Co., Boehringer-Ingelheim Co., and Daiichi-Sankyo Co. The other authors declare no conflicts of interest.

      Author Contributions

      Yuki Katayama, : Software, Validation, Investigation, Visualization Writing - Original Draft; Tadaaki Yamada: Conceptualization, Resources, Writing - Original Draft, Project administration, Methodology, Funding acquisition; Kenji Morimoto: Data Curation; Hiroyuki Fujii: Resources; Satomi Morita, MDa, Keiko Tanimura: Resources; Takayuki Takeda: Resources; Asuka Okada: Resources; Shinsuke Shiotsu: Resources; Yusuke Chihara: Resources; Osamu Hiranuma: Resources; Takahiro Yamada: Resources; Takahiro Ota: Resources; Taishi Harada: Resources; Isao Hasegawa: Resources; Akihiro Yoshimura: Formal analysis; Masahiro Iwasaku: Validation; Shinsaku Tokuda: Validation; Young Hak Kim: Validation; Koichi Takayama: Supervision

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2023.100494

      Copyright

      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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