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Prognostic impact of primary cancer adjoining emphysematous bullae in non-small cell lung cancer patients treated with immune checkpoint inhibitors

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Abstract

Background

Immune checkpoint inhibitors (ICIs) have become a standard therapy in non-small cell lung cancer (NSCLC). Although lung cancer adjoining emphysematous bullae (Ca-ADJ) were reported to express higher programmed cell death-ligand 1 (PD-L1), the predictive impact of Ca-ADJ on the response to ICIs is unknown.

Methods

Two hundred and fifty-seven advanced or recurrent NSCLC patients treated with ICI monotherapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients’ background, adjusted Kaplan–Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed.

Results

Of the 257 patients, 55 had Ca-ADJ. Patients with Ca-ADJ were significantly associated with younger age (P = 0.0343), male sex (P = 0.0070), and smoking (P = 0.0080). The objective response rate of cases with Ca-ADJ was significantly higher than that of those without Ca-ADJ (36.4% vs. 20.8%, respectively; P = 0.0167). The disease control rate of cases with Ca-ADJ was also significantly higher than tumors without Ca-ADJ (63.6% vs. 47.5%, respectively; P = 0.0341). The IPTW-adjusted Kaplan–Meier curves showed that patients with Ca-ADJ had significantly longer progression-free survival (PFS) and overall survival (OS) than those without Ca-ADJ (P = 0.0407 and P = 0.0126, respectively). On IPTW-adjusted Cox analysis, Ca-ADJ was an independent predictor of PFS and OS (P < 0.0001 and P < 0.0001, respectively).

Conclusions

Patients with Ca-ADJ may be good candidates for ICIs. These findings should be validated prospectively.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

Ca-ADJ:

Cancer adjoining emphysematous bullae

EB:

Emphysematous bullae

ECOG PS:

Eastern Cooperative Oncology Group performance status

EGFR:

Epidermal growth factor receptor

ICI:

Immune checkpoint inhibitor

IPTW:

Inverse probability of treatment weights

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PD-L1:

Programmed death-ligand 1

PFS:

Progression-free survival

TMB:

Tumor mutation burden

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Acknowledgements

We thank Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Shinkichi Takamori, Taichi Matsubara, Naoki Haratake, Naoko Miura, Ryo Toyozawa, Masafumi Yamaguchi & Mitsuhiro Takenoyama

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kazuki Takada, Tetsuzo Tagawa & Masaki Mori

  3. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Mototsugu Shimokawa

  4. Department of Radiology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Mikako Jinnnouchi

  5. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yasuto Yoneshima, Kentaro Tanaka & Isamu Okamoto

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  1. Shinkichi Takamori
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Correspondence to Shinkichi Takamori.

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The authors declare no conflicts of interest in association with this study.

Ethical approval

This study was approved by our institutional review boards (Kyushu University, IRB no. 2019–195 and National Hospital Organization Kyushu Cancer Center, IRB no. 2019-45).

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Takamori, S., Takada, K., Shimokawa, M. et al. Prognostic impact of primary cancer adjoining emphysematous bullae in non-small cell lung cancer patients treated with immune checkpoint inhibitors. Cancer Immunol Immunother 70, 1745–1753 (2021). https://doi.org/10.1007/s00262-020-02783-6

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