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Impact of a Ground-glass Opacity Component on c-Stage IA Lung Adenocarcinoma

  • Author Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Ming Li
    Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Junjie Xi
    Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Qihai Sui
    Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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  • Hiroaki Kuroda
    Affiliations
    Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
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  • Kazutoshi Hamanaka
    Affiliations
    Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Nagano, Japan
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  • Stefano Bongiolatti
    Affiliations
    Thoracic Surgery Unit, Careggi University Hospital, Florence, Italy
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  • Goohyeon Hong
    Affiliations
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea
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  • Cheng Zhan
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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  • Mingxiang Feng
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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  • Qun Wang
    Correspondence
    Address reprint requests to Qun Wang, PhD, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No.180, Fenglin Rd, Shanghai 200032, China.
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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  • Lijie Tan
    Affiliations
    Department of Thoracic Surgery, People's Republic of China and Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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  • Author Footnotes
    1 Author Ming Li, Junjie Xi, and Qihai Sui contributed equally to this work.
      Studies have shown that tumors with ground-glass opacity (GGO) components are associated with favorable outcomes. However, this view should be confirmed in an international cohort. We aimed to verify the impact of a GGO component on clinical (c)-stage IA lung adenocarcinoma and to describe the biological discrepancies between the part-solid and pure-solid groups. We evaluated 1333 cases of surgically resected c-stage IA lung adenocarcinomas, including 484 part-solid and 849 pure-solid tumors. Furthermore, we matched the solid size between the 2 groups and examined 470 patients. We compared the prognoses between the 2 groups before and after matching. The prognostic and biological differences were described before and after matching. Compared with the pure-solid group, the part-solid group was associated with favorable outcomes [5-year overall survival (OS) 99.4% vs 87.6%, P < 0.001; 5-year recurrence-free survival (RFS) 96.9% vs 82.2%, P < 0.001]. Similar results were obtained after matching (5-year OS 98.9% vs 92.2%, P = 0.012; 5-year RFS 95.0% vs 88.5%, P = 0.007). Multivariable analyses revealed that GGO component appearance was a factor of better OS and RFS. The part-solid tumor, regardless of the size of the solid component, had a similar outcome to the pure-solid tumor of c-stage T1a classification. Also, more epidermal growth factor receptor, human epidermal growth factor receptor-2 mutations, and receptor tyrosine kinase ROS-1-positive were observed in the part-solid group. In comparison, more wild types and Kirsten-Ras were observed in the pure-solid group. Adenocarcinomas with a GGO component were associated with superior outcomes. The GGO component should be considereda new clinical T descriptor. Early-stage lung adenocarcinomas with and without a GGO component may be 2 distinct tumor types.

      Graphical Abstract

      Keywords

      Abbreviations:

      95% CI (95% confidence interval), AIS (adenocarcinoma in situ), ALK (anaplastic lymphoma kinase), c-Stage (clinical stage), CT (computed tomography), CTR (consolidation/tumor ratio), EGFR (epidermal growth factor receptor), GGO (ground-glass opacity), HER-2 (human epidermal growth factor receptor-2), HRs (hazard ratios), HU (hounsfield units), IQR (interquartile range), JCOG (Japan Clinical Oncology Group), K-Ras (Kirsten-Ras), MIA (minimally invasive adenocarcinoma), NSCLC (non-small cell lung cancer), Nx (lymph node status unknown), OS (overall survival), PET (positron emission tomography), PI3KCA (phosphatidyl-inositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform), pN (pathological lymph node), RFS (recurrence-free survival), TNM (tumor–node–metastasis), VATS (video-assisted thoracic surgery), WHO classification (World Health Organization classification)
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