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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study

Authors: Kota Nakamura, Motoyasu Kato, Takehito Shukuya, Keita Mori, Yasuhito Sekimoto, Hiroaki Ihara, Ryota Kanemaru, Ryo Ko, Rina Shibayama, Ken Tajima, Ryo Koyama, Naoko Shimada, Osamu Nagashima, Fumiyuki Takahashi, Shinichi Sasaki, Kazuhisa Takahashi

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Interstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA.

Methods

Between April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA.

Results

Thirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA.

Conclusions

This is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to determine the risk factors for ILD-AA in advanced lung cancer patients. ΔSP-D might be a serum prognostic biomarker of ILD-AA. Clinicians should evaluate serum SP-D during chemotherapy and should carefully monitor the clinical course in patients with high ΔSP-D.
Literature
1.
go back to reference Kenmotsu H, Naito T, Kimura M, Ono A, Shukuya T, Nakamura Y, Tsuya A, Kaira K, Murakami H, Takahashi T, Endo M, Yamamoto N. The risk of Cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol. 2011;6:1242–6.CrossRefPubMed Kenmotsu H, Naito T, Kimura M, Ono A, Shukuya T, Nakamura Y, Tsuya A, Kaira K, Murakami H, Takahashi T, Endo M, Yamamoto N. The risk of Cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol. 2011;6:1242–6.CrossRefPubMed
2.
go back to reference Hamada T, Yasunaga H, Nakai Y, Isayama H, Matsui H, Fushimi K, Koike K. Interstitial lung disease associated with gemcitabine: a Japanese retrospective cohort study. Respirology. 2016;21:338–43.CrossRefPubMed Hamada T, Yasunaga H, Nakai Y, Isayama H, Matsui H, Fushimi K, Koike K. Interstitial lung disease associated with gemcitabine: a Japanese retrospective cohort study. Respirology. 2016;21:338–43.CrossRefPubMed
3.
go back to reference Sakurada T, Kakiuchi S, Tajima S, Horinouchi Y, Okada N, Nishisako H, Nakamura T, Teraoka K, Kawazoe K, Yanagawa H, Nishioka Y, Minakuchi K, Ishizawa K. Characteristics of and risk factors for interstitial lung disease induced by chemotherapy for lung cancer. Ann Pharmacother. 2015;49:398–404.CrossRefPubMed Sakurada T, Kakiuchi S, Tajima S, Horinouchi Y, Okada N, Nishisako H, Nakamura T, Teraoka K, Kawazoe K, Yanagawa H, Nishioka Y, Minakuchi K, Ishizawa K. Characteristics of and risk factors for interstitial lung disease induced by chemotherapy for lung cancer. Ann Pharmacother. 2015;49:398–404.CrossRefPubMed
4.
go back to reference Kato M, Shukuya T, Takahashi F, Mori K, Suina K, Asao T, Kanemaru R, Honma Y, Muraki K, Sugano K, Shibayama R, Koyama R, Shimada N, Takahashi K. Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease. BMC Cancer. 2014;14:508.CrossRefPubMedPubMedCentral Kato M, Shukuya T, Takahashi F, Mori K, Suina K, Asao T, Kanemaru R, Honma Y, Muraki K, Sugano K, Shibayama R, Koyama R, Shimada N, Takahashi K. Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease. BMC Cancer. 2014;14:508.CrossRefPubMedPubMedCentral
5.
go back to reference Tamiya A, Naito T, Miura S, Morii S, Tsuya A, Nakamura Y, Kaira K, Murakami H, Takahashi T, Yamamoto N, Endo M. Interstitial lung disease associated with Docetaxel in patients with advanced non-small cell lung cancer. Anticancer Res. 2012;32:1103–6.PubMed Tamiya A, Naito T, Miura S, Morii S, Tsuya A, Nakamura Y, Kaira K, Murakami H, Takahashi T, Yamamoto N, Endo M. Interstitial lung disease associated with Docetaxel in patients with advanced non-small cell lung cancer. Anticancer Res. 2012;32:1103–6.PubMed
6.
go back to reference Fujimoto D, Shimizu R, Kato R, Sato Y, Kogo M, Ito J, Teraoka S, Otoshi T, Nagata K, Nakagawa A, Otsuka K, Katakami N, Tomii K. Second-line chemotherapy for patients with small cell lung cancer and interstitial lung disease. Anticancer Res. 2015;35:6261–6.PubMed Fujimoto D, Shimizu R, Kato R, Sato Y, Kogo M, Ito J, Teraoka S, Otoshi T, Nagata K, Nakagawa A, Otsuka K, Katakami N, Tomii K. Second-line chemotherapy for patients with small cell lung cancer and interstitial lung disease. Anticancer Res. 2015;35:6261–6.PubMed
7.
go back to reference Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, Abe M, Nishimura K, Higaki J, Ikezoe J, Kohno N. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003;58:872–5.CrossRefPubMedPubMedCentral Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, Abe M, Nishimura K, Higaki J, Ikezoe J, Kohno N. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003;58:872–5.CrossRefPubMedPubMedCentral
8.
go back to reference Vahid B, Marik PE. Pulmonary complications of novel antineoplastic agents for solid tumors. Chest. 2008;133:528–38.CrossRefPubMed Vahid B, Marik PE. Pulmonary complications of novel antineoplastic agents for solid tumors. Chest. 2008;133:528–38.CrossRefPubMed
9.
go back to reference Takahashi H, Honda Y, Kuroki Y, Imai K, Abe S. Pulmonary surfactant protein a: a serum marker of pulmonary fibrosis in patients with collagen vascular diseases. Clin Chim Acta. 1995;239:213–5.CrossRefPubMed Takahashi H, Honda Y, Kuroki Y, Imai K, Abe S. Pulmonary surfactant protein a: a serum marker of pulmonary fibrosis in patients with collagen vascular diseases. Clin Chim Acta. 1995;239:213–5.CrossRefPubMed
10.
go back to reference Honda Y, Kuroki Y, Matuura E, Nagae H, Takahashi H, Akino T, Abe S. Pulmonary surfactant protein-D in serum and bronchoalveolar lavage fluids. Am J Respir Crit Care Med. 1995;152:1860–6.CrossRefPubMed Honda Y, Kuroki Y, Matuura E, Nagae H, Takahashi H, Akino T, Abe S. Pulmonary surfactant protein-D in serum and bronchoalveolar lavage fluids. Am J Respir Crit Care Med. 1995;152:1860–6.CrossRefPubMed
12.
go back to reference Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S. Serum surfactant proteins a and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000;162:1109–14.CrossRefPubMed Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S. Serum surfactant proteins a and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000;162:1109–14.CrossRefPubMed
13.
go back to reference Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N. Comparative study of KL-6, surfactant protein-a, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med. 2002;165:378–81.CrossRefPubMed Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N. Comparative study of KL-6, surfactant protein-a, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med. 2002;165:378–81.CrossRefPubMed
14.
go back to reference Ishii H, Mukae H, Kadota J, Kaida H, Nagata T, Abe K, Matsukura S, Kohno S. High serum concentrations of surfactant protein a in usual interstitial pneumonia compared with non-specific interstitial pneumonia. Thorax. 2003;58:52–7.CrossRefPubMedPubMedCentral Ishii H, Mukae H, Kadota J, Kaida H, Nagata T, Abe K, Matsukura S, Kohno S. High serum concentrations of surfactant protein a in usual interstitial pneumonia compared with non-specific interstitial pneumonia. Thorax. 2003;58:52–7.CrossRefPubMedPubMedCentral
15.
go back to reference Okamoto T, Fujii M, Furusawa H, Tsuchiya K, Miyazaki Y, Inase N. The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis. Respir Med. 2015;109:1576–81.CrossRefPubMed Okamoto T, Fujii M, Furusawa H, Tsuchiya K, Miyazaki Y, Inase N. The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis. Respir Med. 2015;109:1576–81.CrossRefPubMed
16.
go back to reference Hirasawa Y, Kohno N, Yokoyama A, Kondo K, Hiwada K, Miyake M. Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer. Am J Respir Crit Care Med. 2000;161:589–94.CrossRefPubMed Hirasawa Y, Kohno N, Yokoyama A, Kondo K, Hiwada K, Miyake M. Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer. Am J Respir Crit Care Med. 2000;161:589–94.CrossRefPubMed
17.
go back to reference Ishikawa T, Kubota T, Abe H, Hirose K, Nagashima A, Togashi T, Seki K, Honma T, Yoshida T, Kamimura T. Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C. Hepato-Gastroenterology. 2012;59:2260–3.PubMed Ishikawa T, Kubota T, Abe H, Hirose K, Nagashima A, Togashi T, Seki K, Honma T, Yoshida T, Kamimura T. Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C. Hepato-Gastroenterology. 2012;59:2260–3.PubMed
18.
go back to reference Kashiwabara K, Semba H, Fujii S, Tsumura S, Aoki R. The ratio KL-6 to SLX in serum for prediction of the occurrence of drug-induced interstitial lung disease in lung cancer patients with idiopathic interstitial pneumonias receiving chemotherapy. Cancer Investig. 2015;26:516–21.CrossRef Kashiwabara K, Semba H, Fujii S, Tsumura S, Aoki R. The ratio KL-6 to SLX in serum for prediction of the occurrence of drug-induced interstitial lung disease in lung cancer patients with idiopathic interstitial pneumonias receiving chemotherapy. Cancer Investig. 2015;26:516–21.CrossRef
19.
go back to reference Matsuno O, Ono E, Ueno T, Takenaka R, Nishitake T, Hiroshige S, Miyazaki E, Kumamoto T, Higuchi Y. Increased serum ADAM8 concentration in patients with drug-induced eosinophilic pneumonia -ADAM8 expression depends on the allergen route of entry. Respir Med. 2010;104:34–9.CrossRefPubMed Matsuno O, Ono E, Ueno T, Takenaka R, Nishitake T, Hiroshige S, Miyazaki E, Kumamoto T, Higuchi Y. Increased serum ADAM8 concentration in patients with drug-induced eosinophilic pneumonia -ADAM8 expression depends on the allergen route of entry. Respir Med. 2010;104:34–9.CrossRefPubMed
20.
go back to reference Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med. 1999;160:1843–50.CrossRefPubMed Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med. 1999;160:1843–50.CrossRefPubMed
21.
go back to reference Endo M, Johkoh T, Kimura K, Yamamoto N. Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan thoracic oncology group. Lung Cancer. 2006;52:135–40.CrossRefPubMed Endo M, Johkoh T, Kimura K, Yamamoto N. Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan thoracic oncology group. Lung Cancer. 2006;52:135–40.CrossRefPubMed
22.
go back to reference Hartl D, Griese M. Surfactant protein D in human lung diseases. Eur J Clin Investig. 2006;36:423–35.CrossRef Hartl D, Griese M. Surfactant protein D in human lung diseases. Eur J Clin Investig. 2006;36:423–35.CrossRef
Metadata
Title
Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study
Authors
Kota Nakamura
Motoyasu Kato
Takehito Shukuya
Keita Mori
Yasuhito Sekimoto
Hiroaki Ihara
Ryota Kanemaru
Ryo Ko
Rina Shibayama
Ken Tajima
Ryo Koyama
Naoko Shimada
Osamu Nagashima
Fumiyuki Takahashi
Shinichi Sasaki
Kazuhisa Takahashi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3285-6

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