Models (year) | Clinical characteristics | Radiological characteristics | Variables not included in Fleischner guidelines | Independent predictors of malignancy of SPN in the prediction models | ||||||||
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AGE (mean age) | Sex/race | Smoking history (pack/years) | Family history of lung cancer/history of cancer (%) | Exposure to asbestos, uranium, radon or second-hand smoke | Emphysema/fibrosis/apical scarring/perifissural nodules/multiplicity | Nodule size (diameter mm) | Growth ratea | Morphology/consistency | Location | |||
M. Jacob et al. (2020) [26] | 64.7 ± 12.3 years (≥ 70 years) Benign nodules: 35.4% Malignant nodules: 64.6% | Male or Female/NR | NR | NR/current extra-pulmonary cancer history: 13.9% | NR | NR/Multiple nodules: Benign nodules: 59.1% Malignant nodules: 40.9% | ≤ 30 mm | NR | Margins (Smooth, Lobulated, Spiculated) Calcification Cavitation Sphericity/Solid and subsolid nodules | Central localization | Pleural contact, Air bronchogram, Pulmonary cancer history, Previous TB, Accidental finding, smoking Status. | Age Category, Gender, smoking Status, current Extra pulmonary cancer history, Air bronchogram, nodule size. |
Chen W et al. (2020) [22] | 51.2 ± 10.9 years Benign nodules: 52.9 ± 10.6 years Malignant nodules: 50.6 ± 11.0 years | Male or Female/NR | Exposure to smoking > 6 months, including second-hand smoke Benign nodules: 16.1% Malignant nodules: 5.6% | NR | (See “smoking history”) | NR/ Incisure surrounding nodules: Benign nodules: 16.1% Malignant nodules: 2.5% Multiple nodules: Benign nodules: 76.8% Malignant nodules: 87.5% | ≤ 10 mm | NR | Spiculation, Cavitation sign, Calcification/Solid and subsolid nodules | Left Right Upper Middle Lower | Vascular penetration sign, Pleural adhesions, Long axis, Short axis, Ratio of short-axis to long-axis of the nodule, Nodule density (HU), | Lung nodule density (in HU), vascular penetration sign, nodule type, Incisure surrounding nodules |
Wu Z et al. (2020) [23] | Benign nodules: 51.9 ± 11.8 years Malignant nodules: 59.6 ± 9.5 years | Male or Female/NR | (yes/no) Benign nodules: 33% (yes) Malignant nodules: 51%(yes) | NR | NR | NR | < 30 mm | NR | Smooth margin Calcification Nodule density (Patch, Glass, Dense, Cavity, Soft tissue) Clear border /NR | Upper lobe Other lobes | During of smoking Drinking, Superficial lymphadenopathy, Pleural effusion, Profession, others (RCDW, WBC, PLT, Percentage of lymphocyte, monocyte, and basophil, Albumin, globulin, Fibrinogen) | Age, gender, smoking history, drinking history, smooth margin, calcification, clear border |
Chen et al. (2019) [17] | Benign nodules: 50.35 ± 10.65 years Malignant nodules: 54.92 ± 9.59 years (range 25-75 years) | Male or Female/NR | (yes/no) Benign nodules: 34.05% (yes) Malignant nodules: 33.18% (yes) | Benign nodules: 13.98% Malignant nodules: 16.82%/History of extrathoracic malignant neoplasm (>5 years ago): 4.32% | NR | Emphysema/NR | 8–20 mm | NR | Marginal Spiculation/Solid nodules | ·Upper lobe | Pleural Indentation, BMI, Chronic interstitial or obstructive lung disease, significant enhancement, biomarkers (CEA, CA125, CA199, CA724, NSE, SCC, Ferritin) | Age, marginal spiculation, significant enhancement, and pleural indentation |
Wang et al. (2018) [28] | Benign nodules: 56.19 ± 10.82 years Malignant nodules: 64.22 ± 9.36 years | Male or Female/NR | (yes/no) Benign nodules: 11% (yes) Malignant nodules: 36% (yes) | NR/ History of cancer: benign nodules: 2%, malignant nodules: 11%. | NR | NR | 6–30 mm | NR | Border Lobulation Vascular convergence Pleural retraction Cavity Spiculation Calcification Vacuole Calcification, Spiculation, / Solid and subsolid nodules | RUL RML RLL LUL LLL | Time since quitting, Family cancer history, CT value, SUVmax | Age, lobulation, vascular convergence, pleural retraction, SUVmax |
Yang et al. (2017) [29] | 55.41 ± 11.94 years (Range, 17–87 years) Benign nodules: 49.01 ± 11.88 years Malignant nodules: 58.22 ± 10.83 years | Male or Female/NR | Benign nodules: 41.03 ± 36.58 pack/years Malignant nodules: 36.09 ± 63.51 pack/years Indeterminate nodules: 32.39 ± 20.50 pack/years | NR/Previous medical history of malignancy lung disease: 5% | NR | NR | 4–30 mm | NR | Thin cavitation Thickened cavitation Lobulation Lobulation + spiculation Others: Spiculated protuberances Irregular edge Smooth edge Density Necrosis/ Solid and subsolid nodules | Upper lobe Middle lobe Lower lobe | Previous medical history, extrathoracic disease/ lung Disease excluding malignancy | Gender, age, smoking history, previous extrathoracic disease, previous chronic lung disease except cancer, malignancy history, diameter, lobulation, spiculation, lobulation and spiculation, irregular edges, calcification |
She et al. (2017) [24] | 58.87 ± 10.74 years | Male or Female/NR | NR | NR/History of cancer: 5.2% | NR | Peripheral emphysema/NR | 5–30 mm | NR | Calcification, Spiculation, Cavitation/Solid nodules | ·Left lung ·Upper lobe | Family history of cancer, biomarkers (CEA, SCCA) Pleural indentation | Diameter, cancer history, age, spiculation, pleural indentation, calcification, CEA |
Van Gómez López et al. (2015) [16] | Benign nodules: 58.0±9.1 years Malignant nodules: 64.2±11.1 years | Male or Female/NR | (yes/no) Benign nodules: 27.3% (yes) Malignant nodules: 63.6% (yes) | NR | NR | NR | < 30 mm | NR | NR/NR | NR | – | SUVmax, age |
Zhang et al. (2015) [25] | 55.1±10.7 years | Male or Female/ | Benign nodules: 162.0±47.8 | NR/Previous cancer | NR | NR | ≤ 30 mm | NR | Calcification Spiculation Cavitation | LUL LLL RUL | Family history of cancer, biomarkers | Age, smoking history, diameter, spiculation, clear |
Yang et al. (2017) [29] | 55.41 ± 11.94 years (Range, 17–87 years) Benign nodules: 49.01 ± 11.88 years Malignant nodules: 58.22 ± 10.83 years | Male or Female/NR | Benign nodules: 41.03 ± 36.58 pack/years Malignant nodules: 36.09 ± 63.51 pack/years Indeterminate nodules: 32.39 ± 20.50 pack/years | NR/Previous medical history of malignancy lung disease: 5% | NR | NR | 4–30 mm | NR | Thin cavitation Thickened cavitation Lobulation Lobulation + spiculation Others: Spiculated protuberances Irregular edge Smooth edge Density Necrosis/ Solid and subsolid nodules | Upper lobe Middle lobe Lower lobe | Previous medical history, extrathoracic disease/ lung Disease excluding malignancy | Gender, age, smoking history, previous extrathoracic disease, previous chronic lung disease except cancer, malignancy history, diameter, lobulation, spiculation, lobulation and spiculation, irregular edges, calcification |
She et al. (2017) [24] | 58.87 ± 10.74 years | Male or Female/NR | NR | NR/History of cancer: 5.2% | NR | Peripheral emphysema/NR | 5–30 mm | NR | Calcification, Spiculation, Cavitation/Solid nodules | ·Left lung ·Upper lobe | Family history of cancer, biomarkers (CEA, SCCA) Pleural indentation | Diameter, cancer history, age, spiculation, pleural indentation, calcification, CEA |
Van Gómez López et al. (2015) [16] | Benign nodules: 58.0±9.1 years Malignant nodules: 64.2±11.1 years | Male or Female/NR | (yes/no) Benign nodules: 27.3% (yes) Malignant nodules: 63.6% (yes) | NR | NR | NR | < 30 mm | NR | NR/NR | NR | - | SUVmax, age |
Zhang et al. (2015) [25] | 55.1±10.7 years (Range, 32-80 years) Benign nodules: 50.11±10.15 years Malignant nodules: 61.01±11.36 years | Male or Female/NR | Benign nodules: 162.0±47.8 pieces-year Malignant nodules: 258.9±71.1pieces-year | NR/Previous cancer history: 1.7% | NR | NR | ≤ 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: Pleural retraction sign Clear border Vascular convergence sign/NR | LUL LLL RUL RML RLL | Family history of cancer, biomarkers (CEA, NSE CYFRA 21-1) | Age, smoking history, diameter, spiculation, clear border, CYFRA 21-1 |
Zheng et al. (2015) [18] | Benign nodules: 52.5 ± 12.0 years Malignant nodules: 58.7 ± 11.4 years | Male or Female/NR | Pieces-year ≥ 400 %: Benign nodules: 24.45% Malignant nodules: 19.45% | NR | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: satellite lesions/Subsolid nodules | RUL RML RLL LUL LLL | Haemoglobin, total protein, albumin, ALP, creatinine, LDH, calcium, biomarkers (CEA), family tumour history, BMI, past related diseases, symptoms, FEV1, Pleural tail, central pixel attenuation, enhancement attenuation value, enlarged lymph nodes, pleural effusion | Model with Nodules < 50% GGO: age, symptoms, serum total protein, diameter, lobulation, calcification. Model with Nodules ≥ 50% GGO: sex, FEV1 %, diameter, calcification |
Dong et al. (2013) [15] | 58.12 years (Range, 32–80 years) Benign nodules: 50.11±10.15 years Malignant nodules: 61.01±11.36 years | Male or Female/NR | 468.15 Pieces-year pieces-year Malignant nodules: 258.9±71.1pieces-year | NR/Previous history of history: 1.7% | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: Pleural retraction sign Clear border Vascular convergence sign/NR | LUL LLL RUL RML RLL | Family cancer history, biomarkers (CEA, NSE CYFRA 21-1) | Age, smoking history, CEA, CYFRA 21-1, border, CYFRA 21-1 |
Zheng et al. (2015) [18] | Benign nodules: 52.5 ± 12.0 years Malignant nodules: 58.7 ± 11.4 years | Male or Female/NR | Pieces-year ≥400 %: Benign nodules: 24.45% Malignant nodules: 19.45% | NR | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: satellite lesions/Subsolid nodules | RUL RML RLL LUL LLL | Haemoglobin, total protein, albumin, ALP, creatinine, LDH, calcium, biomarkers (CEA), family tumour history, BMI, past related diseases, symptoms, FEV1, Pleural tail, central pixel attenuation, enhancement attenuation value, enlarged lymph nodes, pleural effusion | Model with Nodules < 50% GGO: age, symptoms, serum total protein, diameter, lobulation, calcification Model with Nodules ≥ 50% GGO: sex, FEV1 %, diameter, calcification |
Dong et al. (2013) [15] | 58.12 years | Male or Female/NR | 468.15 Pieces-year | NR/Previous history of | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation | LUL LLL RUL | Family cancer history, biomarkers | Age, smoking history, CEA, CYFRA 21-1, |
Malignant tumour > 1 year ago:3.45% | Lobulation Others: Clear border Satellite lesions Pleura retraction sign /NR | RML RLL | (NSE, CEA, CYFRA 21-1, CA125, SCC), histological diagnosis malignant | family history of cancer, diameter, lobulation, calcification, spiculation, clear border, satellite lesions | ||||||||
Li et al. (2012) [19] | 57.1 years Benign nodules: 48.0 ± 14.6 years Malignant nodules: 61.2 ± 13.1 years | Male or Female/NR | Benign nodules: 169.8 ± 328.3 pieces-year Malignant nodules: 260.6 ± 410.3 pieces-year | NR/Previous cancer history > 5 years ago: 2.25% | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: Pleural retraction sign Clear border Vascular convergence/NR | Upper lobe Non-upper lobe Left Right | Family history of cancer | Age, diameter, spiculation, family cancer history, calcification, clear border |
Yonemori et al. (2007) [20] | 62 years Benign nodules: 58 years Malignant nodules: 64 years | Male or Female/ NR | Benign nodules: 19 pack-years Malignant nodules: 24 pack-years | NR/Other cancer > 5 years ago: 2.21% | NR | NR | < 30 mm | NR | Calcification Spiculation Cavitation Lobulation Others: CT bronchus sign/NR | LUL Lingular segment LLL RUL RML RLL Right | WCC, serum CRP, biomarkers (CEA) | Calcification, spiculation, Bronchus sign, CEA, CRP |
Gould et al. (2007) [27] | 65.9 ± 10.7 years Benign nodules: 62 years Malignant nodules: 68 years | Male or Female/NR | Benign nodules: 46 pack-years Malignant nodules: 63 pack-years | NR/History of other cancers: 9.06% | NR | NR | 7–30 mm | NR | “definitely malignant”b/NR | Upper lobe /right lung | Number of years since quitting smoking, time since diagnosis of lung/other cancer | Years since quitting smoking, smoking history, age, diameter |
Swensen et al. (1997) [21] | Benign nodules: 60 years (range, 15-82 years) Malignant nodules: 65 years (range, 35-87 years) | Male or Female/NR | Benign nodules: 24 pack-years Malignant nodules: 45 pack-years Indeterminate nodules: 32 pack-years | Of extrathoracic malignancy: 2.86% | 6 subjects with SPN had been exposed to asbestos | NR | 4–30 mm | NR | Calcification, Spiculation, Cavitation, Lobulation Others: Entirely smooth, Spiculated or shaggy/NR | ·Central/peripheral ·Upper lobe ·Location lobe: RUL RML RLL LUL LLL Lingula | Pleural tail, Air bronchogram, residence > 192 km from clinic | Age, history of smoking, Remote history (>5 years) of extrathoracic cancer, diameter, spiculation, upper lobe |