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Prognostic value of CT-defined ground-glass opacity in early-stage lung adenocarcinomas: a single-center study and meta-analysis

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Abstract

Objectives

The prognostic value of ground-glass opacity at preoperative chest CT scans in early-stage lung adenocarcinomas is a matter of debate. We aimed to clarify the existing evidence through a single-center, retrospective cohort study and to quantitatively summarize the body of literature by conducting a meta-analysis.

Methods

In a retrospective cohort study, patients with clinical stage I lung adenocarcinoma were identified, and the prognostic value of ground-glass opacity was analyzed using multivariable Cox regression. Commercial artificial intelligence software was adopted as the second reader for the presence of ground-glass opacity. The primary end points were freedom from recurrence (FFR) and lung cancer-specific survival (LCSS). In a meta-analysis, we systematically searched Embase and OVID-MEDLINE up to December 30, 2021, for the studies based on the eighth-edition staging system. The pooled hazard ratios (HRs) of solid nodules (i.e., absence of ground-glass opacity) for various end points were calculated with a multi-level random effects model.

Results

In a cohort of 612 patients, solid nodules were associated with worse outcomes for FFR (adjusted HR, 1.98; 95% CI: 1.17–3.51; p = 0.01) and LCSS (adjusted HR, 1.937; 95% CI: 1.002–4.065; p = 0.049). The artificial intelligence assessment and multiple sensitivity analyses revealed consistent results. The meta-analysis included 13 studies with 12,080 patients. The pooled HR of solid nodules was 2.13 (95% CI: 1.69–2.67; I2 = 30.4%) for overall survival, 2.45 (95% CI: 1.52–3.95; I2 = 0.0%) for FFR, and 2.50 (95% CI: 1.28–4.91; I2 = 30.6%) for recurrence-free survival.

Conclusions

The absence of ground-glass opacity in early-stage lung adenocarcinomas is associated with worse postoperative survival.

Clinical relevance statement

Early-stage lung adenocarcinomas manifesting as solid nodules at preoperative chest CT, which indicates the absence of ground-glass opacity, were associated with poor postoperative survival. There is room for improvement of the clinical T categorization in the next edition staging system.

Key Points

• In a retrospective study of 612 patients with stage I lung adenocarcinoma, solid nodules were associated with shorter freedom from recurrence (adjusted hazard ratio [HR], 1.98; p = 0.01) and lung cancer-specific survival (adjusted HR, 1.937; p = 0.049).

• Artificial intelligence-assessed solid nodules also showed worse prognosis (adjusted HR for freedom from recurrence, 1.94 [p = 0.01]; adjusted HR for lung cancer-specific survival, 1.93 [p = 0.04]).

• In meta-analyses, the solid nodules were associated with shorter freedom from recurrence (HR, 2.45) and shorter overall survival (HR, 2.13).

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Abbreviations

AI:

Artificial intelligence

EGFR :

Epidermal growth factor receptor

FFR:

Freedom from recurrence

GGO:

Ground glass opacity

HR :

Hazard ratio

LCSS :

Lung cancer-specific survival

PSN :

Part-solid nodule

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Acknowledgements

We sincerely thank Hyun Joon Ahn and Seungho Lee (VUNO Inc.) for their assistance in the data acquisition.

Funding

This study was supported by the Seoul National University Hospital Research Fund (grant number: 04–2020-2040 and 03–2022-2170) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (grant number: NRF-2020R1C1C1003684). However, the funders had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Radiology, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Jong Hyuk Lee, Jin Mo Goo & Hyungjin Kim

  2. Medical Research Collaborating Center, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Yunhee Choi & Hyunsook Hong

  3. Seoul National University Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Young Tae Kim & Jin Mo Goo

  4. Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Young Tae Kim

  5. Department of Radiology, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Jin Mo Goo & Hyungjin Kim

  6. Institute of Radiation Medicine, Seoul National University Medical Research Center, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea

    Jin Mo Goo

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Corresponding author

Correspondence to Hyungjin Kim.

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Guarantor

The scientific guarantor of this publication is Hyungjin Kim.

Conflict of interest

Hyungjin Kim is a member of the European Radiology Editorial Board. They have not taken place in the review or selection process of his article.

Activities not related to the present article: J.H.L. received consulting fees from Radisen; Y.T.K. received consulting fees from Johnson and Johnson; payment for lectures from AstraZeneca; holds stock option in Genome Insight. J.M.G. received research grants from Dongkook Lifescience, LG Electronics, and Coreline Soft. H.K. received a research grant from Lunit; consulting fees from RadiSen; holds stock and stock option in Medical IP.

Statistics and biometry

Two of the authors (Yunhee Choi and Hyunsook Hong) are biostatisticians.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some of the study patients have been reported previously. However, none of the prior studies focused on the prognostic value of ground-glass opacity in lung cancers with freedom from recurrence and/or lung cancer-specific survival as study outcomes.

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

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Lee, J.H., Choi, Y., Hong, H. et al. Prognostic value of CT-defined ground-glass opacity in early-stage lung adenocarcinomas: a single-center study and meta-analysis. Eur Radiol 34, 1905–1920 (2024). https://doi.org/10.1007/s00330-023-10160-x

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