A five-year study of over 900 patients found that small ground-glass lung nodules detected on low-dose CT scans show distinct progressive growth patterns, with family history of lung cancer being a key independent risk factor for nodule growth and potential malignant transformation.
- Only 8.6% of incidental pure ground-glass nodules showed growth over five years, indicating low overall malignancy risk
- Family history of lung cancer was an independent risk factor for nodule growth at both study centers (hazard ratios 2.83-3.94)
- Bubble lucency and vessel sign on CT imaging were additional radiologic features associated with nodule progression
- Current monitoring protocol recommends CT follow-up at 6-12 months to confirm persistence, then every 2 years for up to 5 years
- Researchers recommend integrating machine learning and radiomics for more precise risk stratification and personalized clinical management
Researchers have identified a distinct progressive growth pattern for small pure ground-glass nodules incidentally detected on low-dose chest CT scans, according to a study published August 25 in Radiology.
A group from Wenzhou Medical University in Zhejiang, China, analyzed annual low-dose chest CT scans among 910 patients over five years after small pure ground-glass nodules (< 10 mm) were incidentally detected during routine wellness assessments, and further found the pattern is associated with a family history of lung cancer.
"A family history of lung cancer, alongside other identified radiologic features, can serve as a valuable clinical reference indicator to assist in the risk stratification of incidental subcentimeter [pure ground-glass nodules]," the researchers wrote.
Pure ground-glass nodules are hazy lung opacities on CT that contain no solid component, the authors explained. The widespread adoption of low-dose CT has sharply increased their incidental detection, yet management remains a clinical challenge, they noted. While these nodules carry a lower malignancy risk than solid nodules, a minority undergo "insidious malignant transformation," the group wrote.
The researchers aimed to characterize the long-term growth trajectories of incidental small pure ground-glass nodules, identify independent risk factors for nodule growth and progression, and assess the reproducibility of the findings across independent cohorts.
Serial axial chest CT scans demonstrating the longitudinal evolution of small pure ground-glass nodules (pGGNs) incidentally detected during a routine wellness assessment. (A) Images in a 37-year-old woman with a family history of lung cancer show a nodule with the progressive growth pattern (box). The baseline CT scan, obtained in October 2017, demonstrates a pure ground-glass nodules in the right lower lobe. Consecutive CT scans obtained from 2017 to 2022 show the continuous enlargement of the nodule during active surveillance. The maximum diameter of the nodule increased from 5.6 mm in 2017 to 10.2 mm in 2022. (B) Images in a 45-year-old man show a nodule with the indolent growth pattern (box). The baseline CT scan, obtained in April 2018, demonstrates a pure ground-glass nodules in the left lower lobe. Consecutive CT scans obtained from 2019 to 2023 show that the nodule remained radiographically stable during CT surveillance. The maximum diameter of the nodule was 5.4 mm in 2018 and 6.1 mm at the final surveillance scan in 2023.RSNA
At center 2 (n = 452 nodules), vessel sign (hazard ratio = 2.98; P = 0.04) and family history (hazard ratio = 3.94; P = 0.01) were associated with nodule growth. Latent class trajectory modeling identified a distinct progressive growth pattern in patients from both centers, for which family history of lung cancer was an independent risk factor, the researchers reported.
"Across two independent clinical cohorts, a distinct progressive growth pattern associated with family history of lung cancer was identified in patients with incidental [pure ground-glass nodules detected at low-dose chest CT," the group wrote.
Future studies should focus on integrating the identified clinical growth trajectories with advanced radiomics and machine learning models to enable more precise, individualized risk stratification and clinical management, the researchers concluded.
In an accompanying editorial, Kyung Soo Lee, MD, and Sang-Won Um, MD, both of Sungkyunkwan University in Seoul, South Korea, wrote that the researchers should be commended for providing a remarkably rich longitudinal dataset on pure ground-glass nodules less than 10 mm in diameter followed for five years, and for identifying important conditions that could lead to rapid progression of these nodules.
"In these patients at increased risk for interval growth, CT should be conducted at six to 12 months to confirm persistence, then every two years thereafter for up to 5 years. If solid components or growth develops, surgical lung biopsy should be considered for tissue confirmation," Lee and Um wrote.
The full study is available here.
