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Open Access 01-12-2011 | Research

Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease

Authors: Shigeo Kawase, Noboru Hattori, Nobuhisa Ishikawa, Yasushi Horimasu, Kazunori Fujitaka, Osamu Furonaka, Takeshi Isobe, Seigo Miyoshi, Hironobu Hamada, Takashi Yamane, Akihito Yokoyama, Nobuoki Kohno

Published in: Respiratory Research | Issue 1/2011

Abstract

Background

A high incidence of interstitial lung disease (ILD) has been reported in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), particularly in Japanese populations. A previous report from our laboratory demonstrated that KL-6 was a useful serum biomarker to assess the severity of drug-induced pneumonitis. Based on these observations, this study was conducted to evaluate the risk factors of EGFR-TKIs induced ILD and the usefulness of monitoring serum KL-6 levels in patients who developed EGFR-TKIs induced ILD in a large multi-institutional setting.

Methods

We retrospectively reviewed clinical records and radiographies of 341 patients with advanced NSCLCs who were treated with EGFR-TKIs, and analyzed risk factors for the development of EGFR-TKIs induced ILD. Changes of circulating levels of KL-6 were also evaluated in the patients who developed EGFR-TKIs induced ILD.

Results

Among the 341 patients included in this study, 20 (5.9%) developed EGFR-TKIs induced ILD, and 9 (2.6%) died from ILD. Univariate analyses revealed that only preexisting pulmonary fibrosis was a significant risk factor for the development of EGFR-TKIs induced ILD (p = 0.003). Absolute levels of circulating KL-6 at neither baseline nor the onset of ILD could discriminate between life-threatening and non-life threatening EGFR-TKIs induced ILDs. However, we found that the ratios of serum KL-6 levels just after the onset of EGFR-TKIs induced ILD to those at baseline could quite precisely distinguish survivors from non-survivors (p = 0.006) as well as acute interstitial pneumonia (AIP) pattern from non-AIP pattern (p = 0.005).

Conclusions

The results of this study strongly support the potential of KL-6 as a diagnostic biomarker for life-threatening EGFR-TKIs induced ILD. Monitoring of KL-6 is also useful to evaluate the progression and severity of EGFR-TKIs induced ILD.

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Title: Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease
Authors: Shigeo Kawase
Noboru Hattori
Nobuhisa Ishikawa
Yasushi Horimasu
Kazunori Fujitaka
Osamu Furonaka
Takeshi Isobe
Seigo Miyoshi
Hironobu Hamada
Takashi Yamane
Akihito Yokoyama
Nobuoki Kohno
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2011
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/1465-9921-12-97

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Results

Conclusions

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