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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- 1 Nagoya University, Nagoya, Japan
- 2 Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan
- 3 Nagoya University Hospital, Nagoya, Aichi, Japan
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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