Skip to main content

Advertisement

Log in

Natural progression of persistent pure ground-glass nodules 10 mm or smaller: long-term observation and risk factor assessment

  • Original Article
  • Published:
Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Purpose

Semi-automatic segmentation was used to investigate the natural progression of pure ground-glass nodules (pGGNs) of 5–10 mm in long-term follow-up and to analyze independent risk factors for subsequent growth.

Materials and Methods

A total of 154 pGGNs of 5–10 mm from 132 patients with 698 follow-up CT scans were retrospectively identified. Subsequently, enrolled pGGNs were semiautomatically segmented on initial and follow-up CT to obtain diameter, density and volume, thus calculating mass, volume doubling time (VDT), and mass doubling time (MDT). Kaplan‒Meier analysis and multivariate Cox proportional risk regression were performed to explore independent predictors of pGGN growth. We analyzed growth differences among different pathological results of pGGNs confirmed by surgery. The prognosis was analyzed using the total diameter or solid size of the nodules on the last preoperative CT.

Results

Among the 85 (55.2%) pGGNs with growth, 5.9%, 51.8%, and 80.0% showed growth within 1, 3, and 5 years, respectively. The median VDT and MDT were 1206.4 (range 349.8–5134.4) days and 1161.3 (range 339.4–6630.4) days, respectively. The multivariate Cox risk regression analysis showed that mean CT attenuation (m-CTA) [hazard ratio (HR) = 2.098, p = 0.010] and roundness index (HR = 1.892, p = 0.021) were independent risk factors for pGGN growth. In total, 67.6% of surgically resected and growing pGGNs were invasive non-mucinous adenocarcinoma (IA), including 2 cases of endpoint events, showing a PSN with solid components of 5.6 mm and a solid nodule with a diameter of 19.9 mm.

Conclusions

pGGNs of 5–10 mm showed an indolent clinical course. Follow-up CT imaging of pGGNs in the latter half of the first two years should be a rational management strategy. Small pGGNs with a larger overall m-CTA and roundness index on baseline CT are more likely to grow.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner Society 2017. Radiology. 2017;284(1):228–43.

    Article  PubMed  Google Scholar 

  2. Henschke CI, Yankelevitz DF, Mirtcheva R, McGuinness G, McCauley D, Miettinen OS. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol. 2002;178(5):1053–7.

    Article  PubMed  Google Scholar 

  3. Austin JH, Garg K, Aberle D, Yankelevitz D, Kuriyama K, Lee HJ, et al. Radiologic implications of the 2011 classification of adenocarcinoma of the lung. Radiology. 2013;266(1):62–71.

    Article  PubMed  Google Scholar 

  4. Lee HJ, Goo JM, Lee CH, Yoo CG, Kim YT, Im JG. Nodular ground-glass opacities on thin-section CT: size change during follow-up and pathological results. Korean J Radiol. 2007;8(1):22–31.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee JH, Lim WH, Hong JH, Nam JG, Hwang EJ, Kim H, et al. Growth and clinical impact of 6-mm or larger subsolid nodules after 5 years of stability at chest CT. Radiology. 2020;295(2):448–55.

    Article  PubMed  Google Scholar 

  6. Lee HW, Jin KN, Lee JK, Kim DK, Chung HS, Heo EY, et al. Long-term follow-up of ground-glass nodules after 5 years of stability. J Thorac Oncol. 2019;14(8):1370–7.

    Article  PubMed  Google Scholar 

  7. Lee SW, Leem CS, Kim TJ, Lee KW, Chung JH, Jheon S, et al. The long-term course of ground-glass opacities detected on thin-section computed tomography. Respir Med. 2013;107(6):904–10.

    Article  PubMed  Google Scholar 

  8. Hiramatsu M, Inagaki T, Inagaki T, Matsui Y, Satoh Y, Okumura S, et al. Pulmonary ground-glass opacity (GGO) lesions-large size and a history of lung cancer are risk factors for growth. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2008;3(11):1245–50.

    Article  PubMed  Google Scholar 

  9. Matsuguma H, Mori K, Nakahara R, Suzuki H, Kasai T, Kamiyama Y, et al. Characteristics of subsolid pulmonary nodules showing growth during follow-up with CT scanning. Chest. 2013;143(2):436–43.

    Article  PubMed  Google Scholar 

  10. Silva M, Bankier AA, Centra F, Colombi D, Ampollini L, Carbognani P, et al. Longitudinal evolution of incidentally detected solitary pure ground-glass nodules on CT: relation to clinical metrics. Diagn Interv Radiol (Ankara, Turkey). 2015;21(5):385–90.

    Article  Google Scholar 

  11. Shi Z, Deng J, She Y, Zhang L, Ren Y, Sun W, et al. Quantitative features can predict further growth of persistent pure ground-glass nodule. Quant Imaging Med Surg. 2019;9(2):283–91.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Takahashi S, Tanaka N, Okimoto T, Tanaka T, Ueda K, Matsumoto T, et al. Long term follow-up for small pure ground-glass nodules: implications of determining an optimum follow-up period and high-resolution CT findings to predict the growth of nodules. Jpn J Radiol. 2012;30(3):206–17.

    Article  PubMed  Google Scholar 

  14. Silva M, Sverzellati N, Manna C, Negrini G, Marchianò A, Zompatori M, et al. Long-term surveillance of ground-glass nodules: evidence from the MILD trial. J Thorac Oncol. 2012;7(10):1541–6.

    Article  PubMed  Google Scholar 

  15. Lee JH, Park CM, Lee SM, Kim H, McAdams HP, Goo JM. Persistent pulmonary subsolid nodules with solid portions of 5 mm or smaller: their natural course and predictors of interval growth. Eur Radiol. 2016;26(6):1529–37.

    Article  PubMed  Google Scholar 

  16. Naidich DP, Bankier AA, MacMahon H, Schaefer-Prokop CM, Pistolesi M, Goo JM, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology. 2013;266(1):304–17.

    Article  PubMed  Google Scholar 

  17. Mull RT. Mass estimates by computed tomography: physical density from CT numbers. AJR Am J Roentgenol. 1984;143(5):1101–4.

    Article  CAS  PubMed  Google Scholar 

  18. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011;8(5):381–5.

    Article  PubMed  Google Scholar 

  19. Usuda K, Saito Y, Sagawa M, Sato M, Kanma K, Takahashi S, et al. Tumor doubling time and prognostic assessment of patients with primary lung cancer. Cancer. 1994;74(8):2239–44.

    Article  CAS  PubMed  Google Scholar 

  20. Callister ME, Baldwin DR, Akram AR, Barnard S, Cane P, Draffan J, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015;70(Suppl 2):ii1–54.

    Article  PubMed  Google Scholar 

  21. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.

    Article  CAS  PubMed  Google Scholar 

  22. Han D, Heuvelmans MA, Oudkerk M. Volume versus diameter assessment of small pulmonary nodules in CT lung cancer screening. Translational lung cancer research. 2017;6(1):52–61.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Song YS, Park CM, Park SJ, Lee SM, Jeon YK, Goo JM. Volume and mass doubling times of persistent pulmonary subsolid nodules detected in patients without known malignancy. Radiology. 2014;273(1):276–84.

    Article  PubMed  Google Scholar 

  24. de Hoop B, Gietema H, van de Vorst S, Murphy K, van Klaveren RJ, Prokop M. Pulmonary ground-glass nodules: increase in mass as an early indicator of growth. Radiology. 2010;255(1):199–206.

    Article  PubMed  Google Scholar 

  25. Qi LL, Wu BT, Tang W, Zhou LN, Huang Y, Zhao SJ, et al. Long-term follow-up of persistent pulmonary pure ground-glass nodules with deep learning-assisted nodule segmentation. Eur Radiol. 2020;30(2):744–55.

    Article  PubMed  Google Scholar 

  26. Cho J, Kim ES, Kim SJ, Lee YJ, Park JS, Cho YJ, et al. Long-term follow-up of small pulmonary ground-glass nodules stable for 3 years: implications of the proper follow-up period and risk factors for subsequent growth. J Thorac Oncol. 2016;11(9):1453–9.

    Article  PubMed  Google Scholar 

  27. Eguchi T, Kondo R, Kawakami S, Matsushita M, Yoshizawa A, Hara D, et al. Computed tomography attenuation predicts the growth of pure ground-glass nodules. Lung Cancer. 2014;84(3):242–7.

    Article  PubMed  Google Scholar 

  28. Liang X, Liu M, Li M, Zhang L. Clinical and CT features of subsolid pulmonary nodules with interval growth: a systematic review and meta-analysis. Front Oncol. 2022;12:929174.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kakinuma R, Noguchi M, Ashizawa K, Kuriyama K, Maeshima AM, Koizumi N, et al. Natural history of pulmonary subsolid nodules: a prospective multicenter study. J Thorac Oncol. 2016;11(7):1012–28.

    Article  PubMed  Google Scholar 

  30. Oda S, Awai K, Murao K, Ozawa A, Yanaga Y, Kawanaka K, et al. Computer-aided volumetry of pulmonary nodules exhibiting ground-glass opacity at MDCT. AJR Am J Roentgenol. 2010;194(2):398–406.

    Article  PubMed  Google Scholar 

  31. Borghesi A, Farina D, Michelini S, Ferrari M, Benetti D, Fisogni S, et al. Pulmonary adenocarcinomas presenting as ground-glass opacities on multidetector CT: three-dimensional computer-assisted analysis of growth pattern and doubling time. Diagn Interv Radiol (Ankara, Turkey). 2016;22(6):525–33.

    Article  Google Scholar 

  32. Xia T, Cai M, Zhuang Y, Ji X, Huang D, Lin L, et al. Risk factors for the growth of residual nodule in surgical patients with adenocarcinoma presenting as multifocal ground-glass nodules. Eur J Radiol. 2020;133:109332.

    Article  PubMed  Google Scholar 

  33. Weng Q, Zhou L, Wang H, Hui J, Chen M, Pang P, et al. A radiomics model for determining the invasiveness of solitary pulmonary nodules that manifest as part-solid nodules. Clin Radiol. 2019;74(12):933–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhiyong Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The Institutional Review Board of our hospital approved the retrospective study, and the requirement for informed consent was waived. The ethical approval number is PJ-KS-KY-2022-13.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 322 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, Y., Xiong, Z., Tian, D. et al. Natural progression of persistent pure ground-glass nodules 10 mm or smaller: long-term observation and risk factor assessment. Jpn J Radiol 41, 605–616 (2023). https://doi.org/10.1007/s11604-022-01382-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11604-022-01382-y

Keywords

Navigation