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The extent of ground-glass attenuation is a risk factor of chemotherapy-related exacerbation of interstitial lung disease in patients with non-small cell lung cancer

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Abstract

Objectives

Chemotherapy-related acute exacerbation (AE) of interstitial lung disease (ILD) is observed in certain patients with non-small cell lung cancer (NSCLC) who have ILD. Although the prognosis of AE-ILD is extremely poor, there are no established risk factors for its occurrence. Therefore, we retrospectively investigated whether high-resolution computed tomography (HRCT) findings could identify risk factors for AE-ILD.

Materials and methods

Between January 2005 and December 2016, 35 patients with NSCLC who received chemotherapy at Hiroshima University Hospital and were diagnosed with ILD on HRCT were enrolled. The extent of ground-glass attenuation (GGA), reticulation, honeycomb appearance, and emphysema, as well as the presence of micronodules, traction bronchiectasis, and consolidation were evaluated in five levels of the lung bilaterally. The HRCT scores of GGA, reticulation, honeycomb appearance, and emphysema were determined by the following formula: 100 × sum of the extent of the HRCT findings/lung area.

Results

Thirty-five patients underwent various first- to fifth-line chemotherapy regimens. Nine patients (25.7%) developed AE-ILD. The median HRCT scores of GGA and reticulation were significantly higher in patients with AE-ILD than in those without. On univariate analysis, a GGA area score ≥ 24.8, reticulation area score ≥ 19.5, and KL-6 level ≥ 946 U/mL were significant risk factors. Multivariate logistic analysis revealed that only a GGA area score ≥ 24.8 was an independent risk factor of AE-ILD.

Conclusions

The GGA area on HRCT is a risk factor for chemotherapy-related AE-ILD. Therefore, this parameter can be used to predict the risk of AE-ILD before administering chemotherapy.

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References

  1. Raghu G, Nyberg F, Morgan G (2004) The epidemiology of interstitial lung disease and its association with lung cancer. Br J Cancer 91(Suppl 2):S3–S10

    Article  PubMed  PubMed Central  Google Scholar 

  2. American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161:646–664

    Article  Google Scholar 

  3. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304

    Article  Google Scholar 

  4. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824

    Article  PubMed  PubMed Central  Google Scholar 

  5. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ (2007) Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 176:636–643

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T (2006) Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J 27:143–150

    Article  CAS  PubMed  Google Scholar 

  7. Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, Brown KK (2005) The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 142:963–967

    Article  PubMed  Google Scholar 

  8. Minegishi Y, Takenaka K, Mizutani H, Sudoh J, Noro R, Okano T, Azuma A, Yoshimura A, Ando M, Tsuboi E, Kudoh S, Gemma A (2009) Exacerbation of idiopathic interstitial pneumonias associated with lung cancer therapy. Intern Med 48:665–672

    Article  PubMed  Google Scholar 

  9. Isobe K, Hata Y, Sakamoto S, Takai Y, Shibuya K, Homma S (2010) Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology 15:88–92

    Article  PubMed  Google Scholar 

  10. Shukuya T, Ishiwata T, Hara M, Muraki K, Shibayama R, Koyama R, Takahashi K (2010) Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease. Anticancer Res 30:4357–4361

    CAS  PubMed  Google Scholar 

  11. Minegishi Y, Sudoh J, Kuribayasi H, Mizutani H, Seike M, Azuma A, Yoshimura A, Kudoh S, Gemma A (2011) The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias. Lung Cancer 71:70–74

    Article  PubMed  Google Scholar 

  12. Kinoshita T, Azuma K, Sasada T, Okamoto M, Hattori S, Imamura Y, Yamada K, Tajiri M, Yoshida T, Zaizen Y, Kawahara A, Fujimoto K, Hoshino T (2012) Chemotherapy for non-small cell lung cancer complicated by idiopathic interstitial pneumonia. Oncol Lett 4:477–482

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Choi MK, Hong JY, Chang W, Kim M, Kim S, Jung HA, Lee SJ, Park S, Chung MP, Sun JM, Park K, Ahn MJ, Ahn JS (2014) Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease. Cancer Chemother Pharmacol 73:1217–1225

    Article  CAS  PubMed  Google Scholar 

  14. 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 (2014) Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease. BMC Cancer 14:508

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kenmotsu H, Naito T, Mori K, Ko R, Ono A, Wakuda K, Imai H, Taira T, Murakami H, Endo M, Takahashi T (2015) Effect of platinum-based chemotherapy for non-small cell lung cancer patients with interstitial lung disease. Cancer Chemother Pharmacol 75:521–526

    Article  CAS  PubMed  Google Scholar 

  16. Sekine A, Satoh H, Baba T, Ikeda S, Okuda R, Shinohara T, Komatsu S, Hagiwara E, Iwasawa T, Ogura T, Kato T (2016) Safety and efficacy of S-1 in combination with carboplatin in non-small cell lung cancer patients with interstitial lung disease: a pilot study. Cancer Chemother Pharmacol 77:1245–1252

    Article  CAS  PubMed  Google Scholar 

  17. Non-Small Cell Lung Cancer Collaborative Group (2010) Chemotherapy and supportive care versus supportive care alone for advanced non-small cell lung cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD007309.pub2

  18. Kenmotsu H, Naito T, Kimura M, Ono A, Shukuya T, Nakamura Y, Tsuya A, Kaira K, Murakami H, Takahashi T, Endo M, Yamamoto N (2011) The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol 6:1242–1246

    Article  PubMed  Google Scholar 

  19. Enomoto Y, Inui N, Imokawa S, Karayama M, Hasegawa H, Ozawa Y, Matsui T, Yokomura K, Suda T (2015) Safety of topotecan monotherapy for relapsed small cell lung cancer patients with pre-existing interstitial lung disease. Cancer Chemother Pharmacol 76:499–505

    Article  CAS  PubMed  Google Scholar 

  20. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K (2015) Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia. Cancer Chemother Pharmacol 76:69–74

    Article  CAS  PubMed  Google Scholar 

  21. Asai N, Katsuda E, Hamanaka R, Kosaka K, Matsubara A, Nishimura M, Tanaka H, Yokoe N, Takahashi A, Yamaguchi E, Kubo A (2017) The ATS/ERS/JRS/ALAT statement “IPF by HRCT” could predict acute exacerbation of interstitial lung disease in non-small cell lung cancer. Tumori 103:60–65

    Article  PubMed  Google Scholar 

  22. Ozawa Y, Akahori D, Koda K, Abe T, Hasegawa H, Matsui T, Tanahashi M, Niwa H, Yamada K, Yokomura K, Suda T (2016) Distinctive impact of pre-existing interstitial lung disease on the risk of chemotherapy-related lung injury in patients with lung cancer. Cancer Chemother Pharmacol 77:1031–1038

    Article  CAS  PubMed  Google Scholar 

  23. Sumikawa H, Johkoh T, Colby TV, Ichikado K, Suga M, Taniguchi H, Kondoh Y, Ogura T, Arakawa H, Fujimoto K, Inoue A, Mihara N, Honda O, Tomiyama N, Nakamura H, Muller NL (2008) Computed tomography findings in pathological usual interstitial pneumonia: relationship to survival. Am J Respir Crit Care Med 177:433–439

    Article  PubMed  Google Scholar 

  24. Mura M, Porretta MA, Bargagli E, Sergiacomi G, Zompatori M, Sverzellati N, Taglieri A, Mezzasalma F, Rottoli P, Saltini C, Rogliani P (2012) Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Eur Respir J 40:101–109

    Article  PubMed  Google Scholar 

  25. Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ (2016) Acute exacerbation of idiopathic pulmonary fibrosis. An international working group report. Am J Respir Crit Care Med 194:265–275

    Article  CAS  PubMed  Google Scholar 

  26. Zerhouni E (1989) Computed tomography of the pulmonary parenchyma. An overview. Chest 95:901–907

    Article  CAS  PubMed  Google Scholar 

  27. Kadoch MA, Cham MD, Beasley MB, Ward TJ, Jacobi AH, Eber CD, Padilla ML (2015) Idiopathic interstitial pneumonias: a radiology-pathology correlation based on the revised 2013 American Thoracic Society-European Respiratory Society classification system. Curr Probl Diagn Radiol 44:15–25

    Article  PubMed  Google Scholar 

  28. Sheppard MN, Harrison NK (1992) New perspectives on basic mechanisms in lung disease. 1. Lung injury, inflammatory mediators, and fibroblast activation in fibrosing alveolitis. Thorax 47:1064–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Suzuki H, Sekine Y, Yoshida S, Suzuki M, Shibuya K, Yonemori Y, Hiroshima K, Nakatani Y, Mizuno S, Takiguchi Y, Yoshino I (2011) Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography. Surg Today 41:914–921

    Article  PubMed  Google Scholar 

  30. Reichmann WM, Yu YF, Macaulay D, Wu EQ, Nathan SD (2015) Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis. BMC Pulm Med 15:167

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ishikawa N, Hattori N, Yokoyama A, Kohno N (2012) Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 50:3–13

    Article  PubMed  Google Scholar 

  32. Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K, Kohno N, Bonella F, Guzman J, Costabel U (2014) Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med 108:1031–1039

    Article  PubMed  Google Scholar 

  33. Inata J, Hattori N, Yokoyama A, Ohshimo S, Doi M, Ishikawa N, Hamada H, Kohno N (2007) Circulating KL-6/MUC1 mucin carrying sialyl Lewisa oligosaccharide is an independent prognostic factor in patients with lung adenocarcinoma. Int J Cancer 120:2643–2649

    Article  CAS  PubMed  Google Scholar 

  34. Ishikawa N, Hattori N, Yokoyama A, Tanaka S, Nishino R, Yoshioka K, Ohshimo S, Fujitaka K, Ohnishi H, Hamada H, Arihiro K, Kohno N (2008) Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Int J Cancer 122:2612–2620

    Article  CAS  PubMed  Google Scholar 

  35. Enomoto Y, Inui N, Kato T, Baba T, Karayama M, Nakamura Y, Ogura T, Suda T (2016) Low forced vital capacity predicts cytotoxic chemotherapy-associated acute exacerbation of interstitial lung disease in patients with lung cancer. Lung Cancer 96:63–67

    Article  PubMed  Google Scholar 

  36. Song JW, Hong SB, Lim CM, Koh Y, Kim DS (2011) Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J 37:356–363

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Takeshi Masuda, Yasushi Horimasu, Taku Nakashima, Shintarou Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada & Noboru Hattori

  2. Hiroshima Atomic Bomb Casualty Council, 3-8-6 Sendamachi, Naka-ku, Hiroshima, 730-0052, Japan

    Chihiro Hirano

  3. Department of Emergency and Critical Care Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Shinichiro Ohshimo

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  1. Takeshi Masuda
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  2. Chihiro Hirano
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  3. Yasushi Horimasu
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Correspondence to Takeshi Masuda.

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Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

This retrospective analysis was approved by the Hiroshima University Institutional Review Board (No. E404). All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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To obtain consent of the patients, opt-out method was applied in this retrospective study.

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Masuda, T., Hirano, C., Horimasu, Y. et al. The extent of ground-glass attenuation is a risk factor of chemotherapy-related exacerbation of interstitial lung disease in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 81, 131–139 (2018). https://doi.org/10.1007/s00280-017-3476-5

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  • DOI: https://doi.org/10.1007/s00280-017-3476-5

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