Skip to main content
Top

Open Access 25-04-2024 | Esophageal Cancer | Original Article

Association between interstitial lung abnormality and mortality in patients with esophageal cancer

Authors: Akinori Hata, Masahiro Yanagawa, Tomo Miyata, Yu Hiraoka, Motohiro Shirae, Keisuke Ninomiya, Shuhei Doi, Kazuki Yamagata, Yuriko Yoshida, Noriko Kikuchi, Ryo Ogawa, Hiroto Hatabu, Noriyuki Tomiyama

Published in: Japanese Journal of Radiology

Login to get access

Abstract

Purpose

To investigate the relationship between interstitial lung abnormalities (ILAs) and mortality in patients with esophageal cancer and the cause of mortality.

Materials and methods

This retrospective study investigated patients with esophageal cancer from January 2011 to December 2015. ILAs were visually scored on baseline CT using a 3-point scale (0 = non-ILA, 1 = indeterminate for ILA, and 2 = ILA). ILAs were classified into subcategories of non-subpleural, subpleural non-fibrotic, and subpleural fibrotic. Five-year overall survival (OS) was compared between patients with and without ILAs using the multivariable Cox proportional hazards model. Subgroup analyses were performed based on cancer stage and ILA subcategories. The prevalences of treatment complications and death due to esophageal cancer and pneumonia/respiratory failure were analyzed using Fisher’s exact test.

Results

A total of 478 patients with esophageal cancer (age, 66.8 years ± 8.6 [standard deviation]; 64 women) were evaluated in this study. Among them, 267 patients showed no ILAs, 125 patients were indeterminate for ILAs, and 86 patients showed ILAs. ILAs were a significant factor for shorter OS (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.10–2.55, P = 0.016) in the multivariable Cox proportional hazards model adjusting for age, sex, smoking history, clinical stage, and histology. On subgroup analysis using patients with clinical stage IVB, the presence of ILAs was a significant factor (HR = 3.78, 95% CI 1.67–8.54, P = 0.001). Subpleural fibrotic ILAs were significantly associated with shorter OS (HR = 2.22, 95% CI 1.25–3.93, P = 0.006). There was no significant difference in treatment complications. Patients with ILAs showed a higher prevalence of death due to pneumonia/respiratory failure than those without ILAs (non-ILA, 2/95 [2%]; ILA, 5/39 [13%]; P = 0.022). The prevalence of death due to esophageal cancer was similar in patients with and without ILA (non-ILA, 82/95 [86%]; ILA 32/39 [82%]; P = 0.596).

Conclusion

ILAs were significantly associated with shorter survival in patients with esophageal cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hatabu H, Hunninghake GM, Richeldi L, Brown KK, Wells AU, Remy-Jardin M, et al. Interstitial lung abnormalities detected incidentally on CT: a position paper from the Fleischner society. Lancet Respir Med. 2020;8:726–37.CrossRefPubMedPubMedCentral Hatabu H, Hunninghake GM, Richeldi L, Brown KK, Wells AU, Remy-Jardin M, et al. Interstitial lung abnormalities detected incidentally on CT: a position paper from the Fleischner society. Lancet Respir Med. 2020;8:726–37.CrossRefPubMedPubMedCentral
2.
go back to reference Hata A, Schiebler ML, Lynch DA, Hatabu H. Interstitial lung abnormalities: state of the art. Radiology. 2021;301:19–34.CrossRefPubMed Hata A, Schiebler ML, Lynch DA, Hatabu H. Interstitial lung abnormalities: state of the art. Radiology. 2021;301:19–34.CrossRefPubMed
3.
go back to reference Washko GR, Lynch DA, Matsuoka S, Ross JC, Umeoka S, Diaz A, et al. Identification of early interstitial lung disease in smokers from the COPDGene study. Acad Radiol. 2010;17:48–53.CrossRefPubMed Washko GR, Lynch DA, Matsuoka S, Ross JC, Umeoka S, Diaz A, et al. Identification of early interstitial lung disease in smokers from the COPDGene study. Acad Radiol. 2010;17:48–53.CrossRefPubMed
4.
go back to reference Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364:897–906.CrossRefPubMedPubMedCentral Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364:897–906.CrossRefPubMedPubMedCentral
5.
go back to reference Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.CrossRefPubMedPubMedCentral Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.CrossRefPubMedPubMedCentral
6.
go back to reference Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368:2192–200.CrossRefPubMedPubMedCentral Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368:2192–200.CrossRefPubMedPubMedCentral
7.
go back to reference Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, et al. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology. 2013;268:563–71.CrossRefPubMedPubMedCentral Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, et al. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology. 2013;268:563–71.CrossRefPubMedPubMedCentral
8.
go back to reference Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med. 2016;194:1517–22.CrossRef Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med. 2016;194:1517–22.CrossRef
9.
go back to reference Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315:672–81.CrossRefPubMedPubMedCentral Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315:672–81.CrossRefPubMedPubMedCentral
10.
go back to reference Tominaga J, Bankier AA, Lee KS, Leung AN, Remy-Jardin M, Akira M, et al. Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia. Jpn J Radiol. 2019;37:773–80.CrossRefPubMed Tominaga J, Bankier AA, Lee KS, Leung AN, Remy-Jardin M, Akira M, et al. Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia. Jpn J Radiol. 2019;37:773–80.CrossRefPubMed
11.
go back to reference Iwasawa T, Takemura T, Ogura T. Smoking-related lung abnormalities on computed tomography images: comparison with pathological findings. Jpn J Radiol. 2018;36:165–80.CrossRefPubMed Iwasawa T, Takemura T, Ogura T. Smoking-related lung abnormalities on computed tomography images: comparison with pathological findings. Jpn J Radiol. 2018;36:165–80.CrossRefPubMed
12.
go back to reference Brown SAW, Padilla M, Mhango G, Powell C, Salvatore M, Henschke C, et al. Interstitial lung abnormalities and lung cancer risk in the national lung screening trial. Chest. 2019;156:1195–203.CrossRef Brown SAW, Padilla M, Mhango G, Powell C, Salvatore M, Henschke C, et al. Interstitial lung abnormalities and lung cancer risk in the national lung screening trial. Chest. 2019;156:1195–203.CrossRef
13.
go back to reference Hoyer N, Thomsen LH, Wille MMW, Wilcke T, Dirksen A, Pedersen JH, et al. Increased respiratory morbidity in individuals with interstitial lung abnormalities. BMC Pulm Med. 2020;20:67.CrossRefPubMedPubMedCentral Hoyer N, Thomsen LH, Wille MMW, Wilcke T, Dirksen A, Pedersen JH, et al. Increased respiratory morbidity in individuals with interstitial lung abnormalities. BMC Pulm Med. 2020;20:67.CrossRefPubMedPubMedCentral
14.
go back to reference Axelsson G, Putman R, Aspelund T, Gudmundsson E, Hida T, Araki T, et al. The associations of interstitial lung abnormalities with cancer diagnoses and mortality. Eur Respir J. 2020;56:1902154.CrossRefPubMedPubMedCentral Axelsson G, Putman R, Aspelund T, Gudmundsson E, Hida T, Araki T, et al. The associations of interstitial lung abnormalities with cancer diagnoses and mortality. Eur Respir J. 2020;56:1902154.CrossRefPubMedPubMedCentral
15.
go back to reference Hida T, Hata A, Lu J, Valtchinov VI, Hino T, Nishino M, et al. Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study. Cancer Imaging. 2021;21:14.CrossRefPubMedPubMedCentral Hida T, Hata A, Lu J, Valtchinov VI, Hino T, Nishino M, et al. Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study. Cancer Imaging. 2021;21:14.CrossRefPubMedPubMedCentral
16.
go back to reference Araki T, Dahlberg SE, Hida T, Lydon CA, Rabin MS, Hatabu H, et al. Interstitial lung abnormality in stage IV non-small cell lung cancer: a validation study for the association with poor clinical outcome. Eur J Radiol Open. 2019;6:128–31.CrossRefPubMedPubMedCentral Araki T, Dahlberg SE, Hida T, Lydon CA, Rabin MS, Hatabu H, et al. Interstitial lung abnormality in stage IV non-small cell lung cancer: a validation study for the association with poor clinical outcome. Eur J Radiol Open. 2019;6:128–31.CrossRefPubMedPubMedCentral
17.
go back to reference Iwasawa T, Okudela K, Takemura T, Fukuda T, Matsushita S, Baba T, et al. Computer-aided quantification of pulmonary fibrosis in patients with lung cancer: relationship to disease-free survival. Radiology. 2019;292:489–98.CrossRefPubMed Iwasawa T, Okudela K, Takemura T, Fukuda T, Matsushita S, Baba T, et al. Computer-aided quantification of pulmonary fibrosis in patients with lung cancer: relationship to disease-free survival. Radiology. 2019;292:489–98.CrossRefPubMed
18.
go back to reference Im Y, Park HY, Shin S, Shin SH, Lee H, Ahn JH, et al. Prevalence of and risk factors for pulmonary complications after curative resection in otherwise healthy elderly patients with early stage lung cancer. Respir Res. 2019;20:1–9.CrossRef Im Y, Park HY, Shin S, Shin SH, Lee H, Ahn JH, et al. Prevalence of and risk factors for pulmonary complications after curative resection in otherwise healthy elderly patients with early stage lung cancer. Respir Res. 2019;20:1–9.CrossRef
19.
go back to reference Li F, Zhou Z, Wu A, Cai Y, Wu H, Chen M, et al. Preexisting radiological interstitial lung abnormalities are a risk factor for severe radiation pneumonitis in patients with small-cell lung cancer after thoracic radiation therapy. Radiat Oncol. 2018;13:82.CrossRefPubMedPubMedCentral Li F, Zhou Z, Wu A, Cai Y, Wu H, Chen M, et al. Preexisting radiological interstitial lung abnormalities are a risk factor for severe radiation pneumonitis in patients with small-cell lung cancer after thoracic radiation therapy. Radiat Oncol. 2018;13:82.CrossRefPubMedPubMedCentral
20.
go back to reference Higo H, Kubo T, Makimoto S, Makimoto G, Ihara H, Masaoka Y, et al. Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities. Jpn J Clin Oncol. 2019;49:458–64.CrossRefPubMed Higo H, Kubo T, Makimoto S, Makimoto G, Ihara H, Masaoka Y, et al. Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities. Jpn J Clin Oncol. 2019;49:458–64.CrossRefPubMed
21.
go back to reference Nakanishi Y, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, et al. Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer. Respir Investig. 2019;57:451–9.CrossRefPubMed Nakanishi Y, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, et al. Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer. Respir Investig. 2019;57:451–9.CrossRefPubMed
22.
go back to reference Shimoji K, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, et al. Association of preexisting interstitial lung abnormalities with immune checkpoint inhibitor-induced interstitial lung disease among patients with nonlung cancers. JAMA Netw Open. 2020;3: e2022906.CrossRefPubMedPubMedCentral Shimoji K, Masuda T, Yamaguchi K, Sakamoto S, Horimasu Y, Nakashima T, et al. Association of preexisting interstitial lung abnormalities with immune checkpoint inhibitor-induced interstitial lung disease among patients with nonlung cancers. JAMA Netw Open. 2020;3: e2022906.CrossRefPubMedPubMedCentral
23.
go back to reference Shibaki R, Ozawa Y, Noguchi S, Murakami Y, Takase E, Azuma Y, et al. Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib. Cancer Med. 2022;11:3743–50.CrossRefPubMedPubMedCentral Shibaki R, Ozawa Y, Noguchi S, Murakami Y, Takase E, Azuma Y, et al. Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib. Cancer Med. 2022;11:3743–50.CrossRefPubMedPubMedCentral
24.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.CrossRefPubMed Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.CrossRefPubMed
25.
go back to reference Su M, Ren X, Du D, He H, Zhang D, Xie R, et al. Curcumol β-cyclodextrin inclusion complex enhances radiosensitivity of esophageal cancer under hypoxic and normoxic condition. Jpn J Radiol. 2023;41:1275–89.CrossRefPubMedPubMedCentral Su M, Ren X, Du D, He H, Zhang D, Xie R, et al. Curcumol β-cyclodextrin inclusion complex enhances radiosensitivity of esophageal cancer under hypoxic and normoxic condition. Jpn J Radiol. 2023;41:1275–89.CrossRefPubMedPubMedCentral
26.
go back to reference Miki Y, Takahashi N, Utsunomiya S, Sasamoto R. Relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer. Jpn J Radiol. 2023;41:561–8.CrossRefPubMed Miki Y, Takahashi N, Utsunomiya S, Sasamoto R. Relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer. Jpn J Radiol. 2023;41:561–8.CrossRefPubMed
27.
go back to reference Xu X, Wu Z, Zhang N, Guo Z. Selection of dilution material for non-iodinated iodine as an oral contrast agent for esophageal cancer: a preliminary clinical trial. Jpn J Radiol. 2022;40:1167–74.CrossRefPubMedPubMedCentral Xu X, Wu Z, Zhang N, Guo Z. Selection of dilution material for non-iodinated iodine as an oral contrast agent for esophageal cancer: a preliminary clinical trial. Jpn J Radiol. 2022;40:1167–74.CrossRefPubMedPubMedCentral
28.
go back to reference Kubo K, Wadasaki K, Shinozaki K. Treatment outcomes according to the macroscopic tumor type in locally advanced esophageal squamous cell carcinoma treated by chemoradiotherapy. Jpn J Radiol. 2019;37:341–9.CrossRefPubMed Kubo K, Wadasaki K, Shinozaki K. Treatment outcomes according to the macroscopic tumor type in locally advanced esophageal squamous cell carcinoma treated by chemoradiotherapy. Jpn J Radiol. 2019;37:341–9.CrossRefPubMed
29.
go back to reference Morimoto H, Fujiwara Y, Lee S, Amano K, Hosono M, Miki Y, et al. Treatment results of neoadjuvant chemoradiotherapy followed by radical esophagectomy in patients with initially inoperable thoracic esophageal cancer. Jpn J Radiol. 2018;36:23–9.CrossRefPubMed Morimoto H, Fujiwara Y, Lee S, Amano K, Hosono M, Miki Y, et al. Treatment results of neoadjuvant chemoradiotherapy followed by radical esophagectomy in patients with initially inoperable thoracic esophageal cancer. Jpn J Radiol. 2018;36:23–9.CrossRefPubMed
30.
go back to reference Anbai A, Koga M, Motoyama S, Jin M, Shibata H, Hashimoto M. Outcomes of patients with stage IVA esophageal cancer (Japanese classification) treated with definitive chemoradiotherapy. Jpn J Radiol. 2013;31:270–6.CrossRefPubMed Anbai A, Koga M, Motoyama S, Jin M, Shibata H, Hashimoto M. Outcomes of patients with stage IVA esophageal cancer (Japanese classification) treated with definitive chemoradiotherapy. Jpn J Radiol. 2013;31:270–6.CrossRefPubMed
31.
go back to reference Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, et al. Correction to: recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today. 2020;50:425.CrossRefPubMedPubMedCentral Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, et al. Correction to: recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today. 2020;50:425.CrossRefPubMedPubMedCentral
32.
go back to reference Tseng S-C, Hino T, Hatabu H, Park H, Sanford NN, Lin G, et al. Interstitial lung abnormalities in patients with locally advanced esophageal cancer: prevalence, risk factors, and clinical implications. J Comput Assist Tomogr. 2022;46:871–7.CrossRefPubMedPubMedCentral Tseng S-C, Hino T, Hatabu H, Park H, Sanford NN, Lin G, et al. Interstitial lung abnormalities in patients with locally advanced esophageal cancer: prevalence, risk factors, and clinical implications. J Comput Assist Tomogr. 2022;46:871–7.CrossRefPubMedPubMedCentral
33.
go back to reference Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159.CrossRefPubMed Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159.CrossRefPubMed
34.
go back to reference Axelsson GT, Putman RK, Araki T, Sigurdsson S, Gudmundsson EF, Eiriksdottir G, et al. Interstitial lung abnormalities and self-reported health and functional status. Thorax. 2018;73:884–6.CrossRefPubMed Axelsson GT, Putman RK, Araki T, Sigurdsson S, Gudmundsson EF, Eiriksdottir G, et al. Interstitial lung abnormalities and self-reported health and functional status. Thorax. 2018;73:884–6.CrossRefPubMed
35.
go back to reference Lee JE, Chae KJ, Suh YJ, Jeong WG, Lee T, Kim Y-H, et al. Prevalence and long-term outcomes of CT interstitial lung abnormalities in a health screening cohort. Radiology. 2023;306: e221172.CrossRefPubMed Lee JE, Chae KJ, Suh YJ, Jeong WG, Lee T, Kim Y-H, et al. Prevalence and long-term outcomes of CT interstitial lung abnormalities in a health screening cohort. Radiology. 2023;306: e221172.CrossRefPubMed
37.
go back to reference Chae KJ, Chung MJ, Jin GY, Song YJ, An AR, Choi H, et al. Radiologic-pathologic correlation of interstitial lung abnormalities and predictors for progression and survival. Eur Radiol. 2022;32:2713–23.CrossRefPubMed Chae KJ, Chung MJ, Jin GY, Song YJ, An AR, Choi H, et al. Radiologic-pathologic correlation of interstitial lung abnormalities and predictors for progression and survival. Eur Radiol. 2022;32:2713–23.CrossRefPubMed
38.
39.
go back to reference Noori M, Mahjoubfar A, Azizi S, Fayyaz F, Rezaei N. Immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric and esophageal cancers: a systematic review and meta-analysis. Int Immunopharmacol. 2022;113:109317.CrossRefPubMed Noori M, Mahjoubfar A, Azizi S, Fayyaz F, Rezaei N. Immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric and esophageal cancers: a systematic review and meta-analysis. Int Immunopharmacol. 2022;113:109317.CrossRefPubMed
40.
go back to reference Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, et al. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus. 2022;19:683.CrossRefPubMedPubMedCentral Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, et al. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus. 2022;19:683.CrossRefPubMedPubMedCentral
41.
go back to reference Chae KJ, Lim S, Seo JB, Hwang HJ, Choi H, Lynch D, et al. Interstitial lung abnormalities at CT in the Korean National Lung Cancer screening program: prevalence and deep learning-based texture analysis. Radiology. 2023;307: e222828.CrossRefPubMed Chae KJ, Lim S, Seo JB, Hwang HJ, Choi H, Lynch D, et al. Interstitial lung abnormalities at CT in the Korean National Lung Cancer screening program: prevalence and deep learning-based texture analysis. Radiology. 2023;307: e222828.CrossRefPubMed
Metadata
Title
Association between interstitial lung abnormality and mortality in patients with esophageal cancer
Authors
Akinori Hata
Masahiro Yanagawa
Tomo Miyata
Yu Hiraoka
Motohiro Shirae
Keisuke Ninomiya
Shuhei Doi
Kazuki Yamagata
Yuriko Yoshida
Noriko Kikuchi
Ryo Ogawa
Hiroto Hatabu
Noriyuki Tomiyama
Publication date
25-04-2024
Publisher
Springer Nature Singapore
Published in
Japanese Journal of Radiology
Print ISSN: 1867-1071
Electronic ISSN: 1867-108X
DOI
https://doi.org/10.1007/s11604-024-01563-x