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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Pituitary Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1490042

Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction

Provisionally accepted
Koji Suzuki Koji Suzuki 1,2Tomoko Kobayashi Tomoko Kobayashi 2*Tetsushi Izuchi Tetsushi Izuchi 2*Koki Otake Koki Otake 2*Masahiko Ando Masahiko Ando 3*Tomoko Handa Tomoko Handa 2*Takashi Miyata Takashi Miyata 2*Mariko Sugiyama Mariko Sugiyama 2*Takeshi Onoue Takeshi Onoue 2*Daisuke Hagiwara Daisuke Hagiwara 2*Hidetaka Suga Hidetaka Suga 2*Ryoichi Banno Ryoichi Banno 1*Tetsunari Hase Tetsunari Hase 2*Megumi Inoue Megumi Inoue 2Makoto Ishii Makoto Ishii 2Hiroshi Arima Hiroshi Arima 2*Shintaro Iwama Shintaro Iwama 2*
  • 1 Nagoya University, Nagoya, Japan
  • 2 Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan
  • 3 Nagoya University Hospital, Nagoya, Aichi, Japan

The final, formatted version of the article will be published soon.

    Abstract Background: Immune-related adverse events (irAEs) are reported to be associated with better overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. However, there may be a bias in that patients who develop irAEs must survive long enough to experience the irAEs, and no prospective studies adjusting for immortal time bias (ITB) have examined the relationship between OS and pituitary dysfunction or the two different types of thyroid dysfunction: destructive thyroiditis and hypothyroidism without prior thyrotoxicosis (isolated hypothyroidism). Methods: Patients with NSCLC who received nivolumab or pembrolizumab at Nagoya University Hospital between November 2, 2015 and February 1, 2023 were enrolled. Endocrine irAEs were prospectively assessed during scheduled evaluations of hormone levels. The association between irAE development and survival when considering ITB was examined by time-dependent Cox regression analysis. Results: Of the 194 patients included, 11 (5.7%), 10 (5.2%), and 5 (2.6%) developed pituitary dysfunction, destructive thyroiditis, and isolated hypothyroidism, respectively. The development of pituitary dysfunction (HR 0.36, 95% CI 0.13–0.98, p = 0.045) and destructive thyroiditis (HR 0.31, 95% CI 0.10–0.97, p = 0.044), but not isolated hypothyroidism (HR 1.15, 95% CI 0.42–3.20, p = 0.786), was significantly associated with longer OS. Conclusion: NSCLC patients developing pituitary dysfunction and destructive thyroiditis showed better OS even after adjusting for ITB, suggesting that these irAEs indicate a better prognosis.

    Keywords: Pituitary, Destructive thyroiditis, PD-1, immune checkpoint inhibitors, Immunerelated adverse events

    Received: 02 Sep 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Suzuki, Kobayashi, Izuchi, Otake, Ando, Handa, Miyata, Sugiyama, Onoue, Hagiwara, Suga, Banno, Hase, Inoue, Ishii, Arima and Iwama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Tomoko Kobayashi, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Tetsushi Izuchi, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Koki Otake, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Masahiko Ando, Nagoya University Hospital, Nagoya, 466-8560, Aichi, Japan
    Tomoko Handa, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Takashi Miyata, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Mariko Sugiyama, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Takeshi Onoue, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Daisuke Hagiwara, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Hidetaka Suga, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Ryoichi Banno, Nagoya University, Nagoya, Japan
    Tetsunari Hase, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Hiroshi Arima, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan
    Shintaro Iwama, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Aichi, Japan

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