Multicenter Study

. 2024 May 3;14(1):10162.

doi: 10.1038/s41598-024-60833-w.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Collaborators, Affiliations

Collaborators

Investigators Group for Lung Cancer and IIP:
Y Nakahara, K Ohta, A Gemma, Y Nishizaka, T Ogura, H Kimura, K Nishi, M Nakamura, K Yokomura, H Taniguchi, K Tomii, J Shindo, K Sato, Y Taguchi, H Takahashi, H Takizawa, S Homma, S Nakamura, K Yoshimura, K Usui, K Ichikado, A Bessyo, H Sugiyama, Y Hasegawa, H Nakamura, H Sagara, K Ube, F Nomura, K Kiura, F Yoshiike, K Takahashi, T Kita, H Sakai, M Bando, T Matsumoto, T Inoue, T Kijima, H Mukae, N Masuda, N Matsumoto, F Sakamaki, M Kamimura, A Takise, T Kishaba, Y Nishioka, K Kashiwabara, A Yamamoto, S Fujiuchi, M Shingyoji, M Hanaoka, S Tominaga, J Kadota, T Kasahara, M Motegi, T Harada, S Ishikawa, T Suda, Y Tomizawa, R Hayashi, M Shinoda, M Terada, Y Jin, Y Shikama, T Kikuchi, K Kido, A Yokoyama, S Fuke, H Nagase, H Tanaka, N Hizawa, K Miyazaki, S Ikushima, N Sakai, T Hoshino, M Mishima, H Ohnishi, H Imai, S Nagashima, E Kojima, S Ohishi, Y Ohe, S Iwakami, M Mineshita, Y Komase, H Harada, S Imokawa, H Watanabe, M Ichiki, K Kuwano, N Takahashi, N Chonabayashi, T Hisada, M Yoshida, K Hirata, K Watanabe, Y Sugino, S Yoshioka, H Tomioka, M Aoshima, Y Sugimoto, M Ichinose, S Tamaki, M Tsuchiya, H Katayama, Y Okochi, H Tanaka, K Ogata, T Tsuburai, I Honda

Affiliations

¹ Department of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan. atsushimotty@gmail.com.
² Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. atsushimotty@gmail.com.
³ School of Pharmacy, Department of Clinical Medicine (Biostatistics), Kitasato University, 5-9-1 Shirokane Minato-ku, Tokyo, 108-8642, Japan.
⁴ Department of Respiratory Medicine, National Hospital Organization, Himeji Medical Centre, 68 Hon-machi, Himeji-shi, Hyogo, 670-8520, Japan.
⁵ Department of Respiratory Medicine, National Hospital Organization, Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
⁶ Department of Respiratory Medicine, Japanese Red Cross Osaka Hospital, 5-30 Fudegasakicho, Tennoji-ku, Osaka, 543-8555, Japan.
⁷ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School University, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8602, Japan.
⁸ Department of Respiratory Medicine, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo, 101-8643, Japan.
⁹ Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Centre, 6-16-1 Tomioka-higashi Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0051, Japan.
¹⁰ Department of Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
¹¹ Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
¹² Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
¹³ Department of Pulmonary Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
¹⁴ Department of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan.

PMID: 38702426
PMCID: PMC11068886
DOI: 10.1038/s41598-024-60833-w

Multicenter Study

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Atsushi Miyamoto et al. Sci Rep. 2024.

. 2024 May 3;14(1):10162.

doi: 10.1038/s41598-024-60833-w.

Authors

Collaborators

Investigators Group for Lung Cancer and IIP:
Y Nakahara, K Ohta, A Gemma, Y Nishizaka, T Ogura, H Kimura, K Nishi, M Nakamura, K Yokomura, H Taniguchi, K Tomii, J Shindo, K Sato, Y Taguchi, H Takahashi, H Takizawa, S Homma, S Nakamura, K Yoshimura, K Usui, K Ichikado, A Bessyo, H Sugiyama, Y Hasegawa, H Nakamura, H Sagara, K Ube, F Nomura, K Kiura, F Yoshiike, K Takahashi, T Kita, H Sakai, M Bando, T Matsumoto, T Inoue, T Kijima, H Mukae, N Masuda, N Matsumoto, F Sakamaki, M Kamimura, A Takise, T Kishaba, Y Nishioka, K Kashiwabara, A Yamamoto, S Fujiuchi, M Shingyoji, M Hanaoka, S Tominaga, J Kadota, T Kasahara, M Motegi, T Harada, S Ishikawa, T Suda, Y Tomizawa, R Hayashi, M Shinoda, M Terada, Y Jin, Y Shikama, T Kikuchi, K Kido, A Yokoyama, S Fuke, H Nagase, H Tanaka, N Hizawa, K Miyazaki, S Ikushima, N Sakai, T Hoshino, M Mishima, H Ohnishi, H Imai, S Nagashima, E Kojima, S Ohishi, Y Ohe, S Iwakami, M Mineshita, Y Komase, H Harada, S Imokawa, H Watanabe, M Ichiki, K Kuwano, N Takahashi, N Chonabayashi, T Hisada, M Yoshida, K Hirata, K Watanabe, Y Sugino, S Yoshioka, H Tomioka, M Aoshima, Y Sugimoto, M Ichinose, S Tamaki, M Tsuchiya, H Katayama, Y Okochi, H Tanaka, K Ogata, T Tsuburai, I Honda

Affiliations

¹ Department of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan. atsushimotty@gmail.com.
² Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. atsushimotty@gmail.com.
³ School of Pharmacy, Department of Clinical Medicine (Biostatistics), Kitasato University, 5-9-1 Shirokane Minato-ku, Tokyo, 108-8642, Japan.
⁴ Department of Respiratory Medicine, National Hospital Organization, Himeji Medical Centre, 68 Hon-machi, Himeji-shi, Hyogo, 670-8520, Japan.
⁵ Department of Respiratory Medicine, National Hospital Organization, Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
⁶ Department of Respiratory Medicine, Japanese Red Cross Osaka Hospital, 5-30 Fudegasakicho, Tennoji-ku, Osaka, 543-8555, Japan.
⁷ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School University, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8602, Japan.
⁸ Department of Respiratory Medicine, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo, 101-8643, Japan.
⁹ Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Centre, 6-16-1 Tomioka-higashi Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0051, Japan.
¹⁰ Department of Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
¹¹ Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
¹² Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
¹³ Department of Pulmonary Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
¹⁴ Department of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan.

PMID: 38702426
PMCID: PMC11068886
DOI: 10.1038/s41598-024-60833-w

Abstract

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

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Conflict of interest statement

Atsushi Miyamoto received a lecture fee from Boehringer Ingelheim Japan Inc.; Takashi Ogura received honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Japan Boehringer Ingelheim and Shionogi Co., and participating on the data safety monitoring board or advisory board of BMS, Japan Boehringer Ingelheim, and Taiho Pharmaceutical Co., Ltd.; Yuji Minegishi received honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from AstraZeneca K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb Company, Takeda Pharmaceutical Co. Ltd., Eisai Co. Ltd., Boehringer Ingelheim Japan Inc., Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., and Nippon Kayaku Co. Ltd.; Kazuhisa Takahashi received honoraria for lectures, presentations and speakers from Nippon Boehringer Ingelheim Co. Ltd., MSD K.K., Pfizer Inc., AstraZeneca K.K., TAIHO PHARMACEUTICAL CO., LTD., KYORIN Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., ONO PHARMACEUTICAL CO., LTD., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd., Bristol Myers K.K., Meiji Seika Pharma Co., Ltd., Takeda Pharmaceutical Company Limited., Viatris Inc., Janssen Pharmaceutical K.K., Abbott Japan LLC., Thermo Fisher Scientific Inc. and Chugai Pharmaceutical Co., Ltd.; grants from NIPPON SHINYAKU CO., LTD., TSUMURA & CO., Pfizer Inc., ONO PHARMACEUTICAL CO., LTD., Novartis Pharma Inc., SHIONOGI & CO., LTD., DAIICHI SANKYO Co., LTD., NIPRO PHARMA CORPORATION, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Bayer Yakuhin, Ltd, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., KYORIN Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., TAIHO PHARMACEUTICAL CO., LTD., and TEIJIN PHARMA LIMITED; leadership role in society, committee or advocacy group of the Japan Lung Cancer Society and the Japanese Respiratory Society.; Hirofumi Michimae, Yasuharu Nakahara, Shinobu Akagawa, Kazuhiko Nakagawa, Yuji Minegishi, Shigeto Hontsu, Hiroshi Date, Sakae Homma, and Kazuma Kishi have no conflicts of interest.

Figures

**Figure 1**
Flow chart for patients’ selection of this study.

**Figure 2**
Landmark analysis. Kaplan–Meier survival curve for comparison of the group which experienced acute exacerbation (AE group) with one which did not experience acute exacerbation (no AE group) during the first-line chemotherapy with landmark points of (a) 30, (b) 60, (c) 90, and (d) 120 days, respectively, after the date of administration of the first-line regimen.

**Figure 3**
Kaplan–Meier survival curve for subgroups of NSCLC (n = 492) and SCLC (n = 216) with median survival time and 1, 2, 3 and 4 year-survival rates.

See this image and copyright information in PMC

References

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Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Collaborators

Affiliations

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources