Table 2.
Summary of studies on the natural history of persistent Subsolid Nodules.
| Author, Publication Year, and Reference No. | Country/Type of study | Patients/No. of nodules | Type of SSN/No. of nodules | Size of baseline SSNs (mm) | Follow-up period (month) | Growth definition and pattern | Time to progression (month) | Progression proportion (%) | Risk factors of SSNs progress | Note |
|---|---|---|---|---|---|---|---|---|---|---|
| Kim YW et al., 2021 (13) | Korea/Single-center, retrospective | 4545/6725 | pGGN 5116 mGGN 1609 |
pGGN 6.1 ± 2.1 mGGN 9.7 ± 5.2 |
Median, 35.1 (range, 13.7–58.5) | pGGN: De (n = 1317), I+IS+NS (n = 160); mGGN: De (n = 799), I+IS+NS (n = 130) |
NA | pGGN 4.6% mGGN 9.2% |
age, initial diameter, initial presentation as a part-solid nodule | SSNs detected at baseline and new-onset |
| Gao C et al., 2020 (34) | China/Single-center, retrospective | 85/110 | pGGN 83 mGGN 27 |
total 8.1 ± 3.8 | ≥24 | NA | NA | pGGN 24.1% mGGN 59.2% |
Lung-rad score, the initial diameter | SSNs followed for > 2 years |
| Qi LL et al., 2020 (35) | China/Single-center, retrospective | 110/110 | pGGN 110 | 8.7 ± 3.2 | 48.7 ± 23.8 | pGGN: V (n = 52) | 28.4 ± 22.5 (range, 3.8-95.5) | 47.30% | lobulated sign, initial mean diameter, initial volume, initial mass | Persistent pGGNs follow-up of ≥ 2 years and those with a follow-up of < 2 years but that had grown |
| Lee JH et al., 2020 (36) | Korea/Single-center, retrospective | 235/235 | pGGN 211 mGGN 24 | pGGN 8 ± 1 (range, 6–13) mGGN 9 ± 3 (range, 7–17) | Median, 112 (range, 84–208) | pGGN: I (n = 2), NS (n = 1); mGGN: IS (n = 2) |
Median, 99 (range, 84-146) | pGGN 1.42% mGGN 8.3% | NA | GGNs with stability for 5 years and follow-up for at least 2 years, GGNs≥6 mm |
| Lee HW et al., 2019 (37) | Korea/Single-, center, retrospective | 160/208 | pGGN 162 mGGN 46 | GGNs 4.7 (range, 1.7–10.0) solid component 2.1 (range,0.9–5.7) | Median, 136 (range, 120–179) | I+DS (n = 16); I (n = 11) | Median, 103 (range, 60–141) | pGGN 11.7% mGGN 17.4% | bubble lucency, history of cancer other than lung cancer, development of a new solid component | Stable for 5 years and follow-up for at least 5 years, 76% (159/208) of GGNs<6 mm, 70% of growing GGNs (19/27) <6 mm |
| Sawada S et al., 2017 (38) | Japan/Single-center, retrospective | 226/226 | pGGN 164 mGGN 35 |
Median, 10 (range, 3-30) | NA | NA | Median, 24 (range, 3-108) | total 17.3% | CTR | SSNs ≤ 30 mm |
| Tang EK et al., 2019 (39) | China/Single-center, retrospective | 128/128 | pGGN 93 mGGN 35 |
pGGN 7.14 ± 4.52, mGGN 17.52 ± 8.65 | 42.84 ± 35.16 | pGGN: TG (n=37), SG (n = 17), SS (n = 4); mGGN: TG (n=37), SG (n = 17), SS (n = 4); | TG: Mean pGGN: 83.4, mGGN:47.5 SG: Mean pGGN: 113.1, mGGN:47.5 SS: Mean pGGN: 146.0, mGGN:86.4 |
TG: pGGN: 40.0%, mGGN:65.7% SG: pGGN: 18.2%, mGGN: 65.7% SS: Mean pGGN: 4.3%, mGGN:17.4% |
older age, PSN nodule type, longer follow-up time | NA |
| Cho J et al., 2016 (40) | Korea/Single-centre, retrospective | 218/453 | pGGN 438 mGGN 15 | Median, 5.0 (range, 2.0–31.1) |
Median, 77.5 (38.1–117.1) | pGGN: I + NS (n = 1), NS + De (n = 1); mGGN: I + IS (n = 1); I (n = 12) | VDT 39.9(19.1-349.5) | total 3.3% | age 65 years or older, history of lung cancer, initial size 8 mm or larger, presence of a solid component, air bronchogram | Stable for 3 years and follow-up for at least 2 years |
| Kakinuma R et al., 2016 (26) | Japan/Multicenter, prospective | 795/1229 | pGGN 1046 hGGN 81 PSN 104 |
Median, 7.0 (IQR 5.5–9.0) | 51.6 ± 30 (Median 42, IQR 28.8–72years) | NA | pGGN 45.6 ± 24 hGGN 25.2 ± 27.6 |
pGGN 16.6% hGGN 19.8% |
initial diameter | SSNs ≤ 30 mm confirmed as persistent on follow-up |
| Scholten ET et al., 2015 (7) | Netherland/Multicenter, prospective | 108/117 | pGGN 69 mGGN 48 |
pGGN 11.1 ± 3.6 (range, 5.1–22.6) mGGN 12.7 ± 6.2 (range, 4.6–34.3) |
Median, 95 (range 20–110) | pGGN: M (n = 26); mGGN: M (n = 35) | MDT<13.3 months 8.9%, MDT>13.3 months 51.4% | increase in mass≥30% pGGN 63.4%, mGGN 58.3% |
NA | SSNs detected by NELSON |
| Eguchi T et al., 2014 (41) | Japan/Single-center, retrospective | 124/124 | pGGN 124 | 7.4 ± 2.8 | Median, 57.0 (range, 24.1–113.6) | pGGN: NS (n = 40), I (n = 24) | Median, 38.0 (range 3.1–80.0) | 51.61% | smoking history, initial tumor size, the mean CT attenuation value | SSNs followed for > 2 years |
| Song YS et al., 2014 (23) | Korea/Single-center, retrospective | 97/97 | pGGN 63 mGGN with solid parts ≤5mm 23 mGGN with solid parts >5mm 11 |
pGGN: Median, 8.3 (range, 5.5-22.2) mGGN with solid parts ≤5mm: Median, 11.1 (range, 6.5-19.3) mGGN with solid parts >5mm: Median, 18.8 (range, 14.5-23.8) |
Median, 21.1 (range, 3.1–89.0) | pGGN: V (n = 12), M (n = 26); mGGN: V (n = 17), M (n = 20) | VDT:pGGN: Median, 61.1 (range, 41.0–151.0) mGGN with solid parts ≤5mm: Median, 40.9 (range, 31.2–153.9) mGGN with solid parts >5mm: Median, 25.3 (range, 12.5–31.4) |
pGGN 27.0% mGGN with solid parts ≤5mm 39.1% mGGN with solid parts >5mm 81.8% |
NA | NA |
| Kobayashi Y et al., 2014 (42) | Japan/Single-center, retrospective | 67/120 | pGGN 91 mGGN 29 |
Total: Median, 9 (range, 4–24) | Median, 50.4 (range, 6–144) | pGGN: D (n = 20); mGGN: D (n = 14) | within 36 months | pGGN 16.48% mGGN 65.52% |
Smoking history, initial lesion diameter | The inclusion criteria for mGGN is that the solid component ≤ 50% |
| Kobayashi Y et al., 2013 (43) | Japan/Single-centre, retrospective | 61/108 | pGGN 82, mGGN 26 | 9.5 (range, 4–25) | Median, 50.4 | SSN: I (n = 15); mGGN: I+ IS (n = 14) | NA | total 26.8% | NA | GGNs ≤ 30 mm confirmed as persistent on follow-up |
| Chang B et al., 2013 (29) | Korea/Single-center, retrospective | 89/122 | pGGN 122 | Median, 5.5 (range, 3.0-20.0) | Median, 59 (range, 25-140) | pGGN: I (n = 12) | VDT: median, 25.6 (range, 11-101) | GGNs 9.8% People 13.5% |
initial diameter, internal solid portion | pGGNs followed for > 2 years |
| Silva M et al., 2012 (8) | Italy/Multicenter, prospective | 56/76 | pGGN 48 mGGN 28 |
7.0 ± 2.0 | 50.26 ± 7.3 | pGGN: DS (n = 0), D (n = 7), D+DS (n = 1); mGGN: DS (n = 3), D (n = 5), D+DS (n = 4); | NA | pGGN 16.7% mGGN 46.2% |
NA | SSNs detected by MLID |
| Hiramatsu M et al., 2008 (44) | Japan/Single-center, retrospective | 125/125 | pGGN 95, mGGN 30 | Total: Mean 8.3 (range, 3.0-17.0) | Mean, 34.9 (range, 5.9-109.0) | pGGN: D (n = 8), NS (n = 6); mGGN: D (n = 5), DS (n = 7) | Growth incidence at 3 and 5 years were estimated to be 18% and 30%, respectively | pGGN 14.74% mGGN 40.0% |
the initial size, history of lung cancer. | SSNs were stable for 3 months |
pGGN, pure ground-glass nodule; mGGN, mixed ground-glass nodule; hGGN, heterogeneous ground-glass nodule; PSN, part-solid nodule; SSN, subsolid nodule; IQR, interquartile range; VDT, volume double time; MDT, mass double time; NELSON, Nederlands Leuvens Longkanker Screenings Onderzoek; MILD, Multicentric Italian Lung Detection trial; I, increase in mean/longest diameter≥2mm; IS, increase in the solid portion of 2mm or more; NS, the emergence of a new solid component; 3D, increase in 3D diameter≥2mm; V, increase in volume by at least 20% or 25%; V/M, an increase of at least 30% in volume or mass; De, nodules that disappeared, or exhibited a decrease of ≥2 mm in the total size or solid portion; TG, true growth was defined as I+IS+NS; SG, substantial growth was defined as an obvious increase of ≧ 5 mm or more in SSNs, the solid portion in PSN increased by 5 mm or more from the baseline; SS, stage shift was defined as the specific stage shift of LUAD diagnosed to detect obvious different categories/stages shift according to the seventh lung cancer TNM staging system based on their clinical and pathologic information at the presentation of follow-up CT scan from the baseline.