Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Inclusion
2.2. Data Collection and Definitions
2.3. Statistical Analysis
3. Results
3.1. Study Population and Baseline Characteristics
3.2. Univariate Analysis Identified 29 Predictive Factors for Lymphoma
3.3. Multivariate Analysis Creates a Diagnostic Model for Predicting Lymphoma
Added Value of the Model Compared to the Literature
3.4. Added Value of TARC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
List of Abbreviations
ALCL | Anaplastic large cell lymphoma |
AUC | Area under the curve |
BL | Burkitt lymphoma |
B-LBL | B-cell lymphoblastic lymphoma |
cHL | Classical Hodgkin lymphoma |
CI | Confidence interval |
CRP | C-reactive protein |
CV | Cross validation |
DLBCL | Diffuse large B-cell lymphoma |
ELISA | Enzyme-linked immunosorbent assay |
ESR | Erythrocyte sedimentation rate |
LD | Lactate dehydrogenase |
NHL | Non-Hodgkin lymphoma |
NLPHL | Nodular lymphocyte-predominant Hodgkin lymphoma |
OR | Odds ratio |
PMBCL | Primary mediastinal large B-cell lymphoma |
PTGC | Progressive transformation of germinal centers |
PTLD | Post-transplant lymphoproliferative disorders |
ROC | Receiver operating characteristic |
TARC | Thymus and activation regulated chemokine |
T-LBL | T-cell lymphoblastic lymphoma |
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Characteristics Malignant Group | Study Group, Malignant n = 115 | Test Group, Malignant n = 40 | Differences between Malignant Groups, p-Value | Differences between Test Group and Study Group in Total p-Values |
Gender | - | - | 0.72 | 0.88 |
Male (%) | 67 (58.2) | 22 (55.0) | - | - |
Female (%) | 48 (41.7) | 18 (45.0) | - | - |
Age median (range) | 14.0 (1–18) | 14.2 (2–18) | 0.53 | 0.80 |
Diagnoses (%) | - | - | 0.26 | - |
Hodgkin lymphoma | 90 (78.3) | 29 (72.5) | - | - |
cHL | 79 | 26 | - | - |
NLPHL | 11 | 3 | - | - |
Non-Hodgkin lymphoma | 24 (20.9) | 11 (27.5) | - | - |
ALCL | 5 | 1 | - | - |
PMBCL | 1 | 0 | - | - |
DLBCL | 3 | 1 | - | - |
BL | 5 | 0 | - | - |
T-LBL | 8 | 9 | - | - |
B-LBL | 2 | 0 | - | - |
Other malignancy | 1 (0.9) | 0 (0.0) | - | - |
Histiocytosis | 1 | 0 | - | - |
Isolated lymphadenopathy (%) * | 8 (6.9) | 3 (7.5) | 0.91 | 1.00 |
cHL | - | 1 | - | - |
NLPHL | 8 | 2 | - | - |
Characteristics Benign Group | Study Group, Benign n = 67 | Test Group, Benign n = 20 | Differences between Benign Groups, p-Value | Not Applicable |
Gender | - | 0.95 | - | |
Male (%) | 33 (49.3) | 10 (50.0) | - | - |
Female (%) | 34 (50.7) | 10 (50.0) | - | - |
Age median (range) | 12.5 (0–17) | 13.5 (1–18) | 0.51 | - |
Diagnoses (%) | - | 0.19 | - | |
Reactive/infective lymphadenopathy | 48 | 15 | - | - |
Immunological disorder | 5 | 2 | - | - |
PTGC | 4 | 2 | - | - |
Morbus Castleman | 2 | - | - | - |
Rheumatological disorder | 2 | - | - | - |
Ruptured branchiogenic cyst | 3 | - | - | - |
Venous malformation | 1 | 1 | - | - |
Lymphangioma | 1 | - | - | - |
Dermoid cysts | 1 | - | - | - |
Isolated lymphadenopathy (%) * | 21 (31.3) | 6 (30.0) | 0.91 | - |
Reactive/infective lymphadenopathy | 13 | 5 | - | - |
PTGC | 1 | - | - | - |
Morbus Castleman | 1 | - | - | - |
Ruptured branchiogenic cyst | 3 | - | - | - |
Venous malformation | 1 | 1 | - | - |
Lymphangioma | 1 | - | - | - |
Dermoid cysts | 1 | - | - | - |
Variables | Malignant Group (n = 115) | Benign Group (n = 67) | Total (n = 182) | Outcome Univariate Analysis | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
n | (%) | m | n | (%) | m | n | (%) | p Value | OR | 95% CI | |
Age | |||||||||||
0–5 years | 10 | 9 | 0 | 22 | 33 | 0 | 32 | 18 | <0.001 | ||
6–12 years | 37 | 32 | 15 | 22 | 52 | 29 | |||||
13–18 years | 68 | 59 | 30 | 45 | 98 | 55 | |||||
Gender | |||||||||||
Male | 67 | 58 | 0 | 33 | 49 | 0 | 100 | 55 | 0.28 | 1.44 | (0.79–2.64) |
Female | 48 | 42 | 34 | 51 | 82 | 45 | |||||
Lymph nodes ultrasound | |||||||||||
Pathological lymph nodes a | 101 | 96 | 10 | 24 | 37 | 2 | 125 | 74 | <0.001 | 43.14 | (14.09–132.07) |
No/uncertain pathological lymph nodes | 4 | 4 | 41 | 63 | 45 | 27 | |||||
Cervical levels involved in accordance with Robbins Classification [49] | |||||||||||
Level I | 15 | 14 | 11 | 11 | 18 | 6 | 26 | 16 | 0.51 | 0.75 | (0.32–1.76) |
Level II | 60 | 57 | 46 | 75 | 106 | 64 | 0.02 | 0.43 | (0.21–0.86) | ||
Level III | 62 | 58 | 23 | 38 | 85 | 51 | 0.01 | 2.33 | (1.22–4.44) | ||
Level IV | 91 | 86 | 18 | 30 | 109 | 65 | <0.001 | 14.49 | (6.67–31.47) | ||
Level V | 68 | 64 | 15 | 25 | 83 | 50 | <0.001 | 5.5 | (2.71–11.11) | ||
Level VI | 24 | 23 | 3 | 5 | 27 | 16 | 0.002 | 5.66 | (1.63–19.68) | ||
Number of involved cervical levels | |||||||||||
>3 levels involved | 36 | 32 | 11 | 4 | 6 | 6 | 40 | 22 | <0.001 | 7.27 | (2.46–21.51) |
Cervical involvement | |||||||||||
Unilateral | 36 | 34 | 11 | 43 | 67 | 3 | 79 | 47 | <0.001 | 3.98 | (2.06–7.69) |
Bilateral | 70 | 66 | 21 | 33 | 91 | 54 | |||||
Size lymph nodes level I, II, III (short axis) | |||||||||||
>15 mm | 22 | 77 | 0 | 14 | 42 | 0 | 36 | 56 | 0.03 | 3.31 | (1.18–9.37) |
Size lymph nodes level IV, V, VI (short axis) | |||||||||||
>10 mm | 44 | 92 | 1 | 6 | 60 | 1 | 58 | 86 | 0.024 | 7.33 | (1.44–37.22) |
Size non-cervical lymph nodes (short axis) | |||||||||||
>10 mm | 10 | 83 | 2 | 2 | 50 | 0 | 12 | 75 | 0.52 | 5.00 | (0.42–59.68) |
Thorax abnormalities | |||||||||||
Enlarged mediastinum | 64 | 56 | 0 | 2 | 3 | 4 | 66 | 37 | <0.001 | 38.28 | (8.93–164.10) |
Obstructed airway | 32 | 28 | 1 | 2 | 33 | 19 | <0.001 | 23.90 | (3.18–179.72) | ||
Trachea deviation | 22 | 19 | 1 | 2 | 23 | 13 | <0.001 | 14.67 | (1.93–111.63) | ||
V. cava superior syndrome | 20 | 17 | 0 | 0 | 20 | 11 | <0.001 | 0 | NA | ||
Enlarged liver and/or spleen | |||||||||||
No abnormalities | 71 | 62 | 1 | 47 | 90 | 15 | 118 | 71 | <0.001 | 5.69 | (2.10–15.43) |
Abnormal | 43 | 38 | 5 | 10 | 48 | 29 | |||||
Body regions involved (presence of pathological lymph node or mass) | |||||||||||
High cervical | 108 | 94 | 0 | 64 | 96 | 0 | 172 | 95 | 0.75 | 0.72 | (0.18–2.89) |
Supraclavicular | 97 | 84 | 19 | 28 | 116 | 64 | <0.001 | 13.61 | (6.55–28.29) | ||
Infraclavicular | 39 | 34 | 0 | 0 | 39 | 21 | <0.001 | 0 | NA | ||
Axilla | 39 | 34 | 8 | 12 | 47 | 26 | 0.001 | 3.79 | (1.65–8.71) | ||
Mediastinal | 90 | 78 | 5 | 8 | 95 | 52 | <0.001 | 44.64 | (16.21–122.96) | ||
Abdominal lymph nodes | 40 | 35 | 9 | 13 | 49 | 27 | 0.002 | 3.44 | (1.54–7.65) | ||
Other locations | 69 | 60 | 16 | 24 | 85 | 47 | <0.001 | 4.78 | (2.44–9.38) | ||
Number of body regions involved | |||||||||||
>3 involved | 78 | 68 | 0 | 8 | 12 | 0 | 86 | 47 | <0.001 | 15.55 | (6.74–35.86) |
Laboratory values | |||||||||||
ESR > 16.5 mm/h b | 77 | 72 | 8 | 28 | 43 | 2 | 105 | 61 | <0.001 | 3.39 | (1.77–6.48) |
Hb < 8.15 g/dL c | 82 | 71 | 0 | 39 | 58 | 0 | 121 | 67 | 0.08 | 1.78 | (0.95–3.36) |
Leukocytes > 8.35 (×103/mm3) c | 73 | 64 | 0 | 31 | 46 | 0 | 104 | 57 | 0.03 | 2.02 | (1.09–3.72) |
Neutrophils > 6.0 (×103/mm3) b | 58 | 51 | 1 | 9 | 14 | 1 | 67 | 37 | <0.001 | 6.56 | (2.97–14.49) |
Lymphocytes < 2.6 (×103/mm3) b | 87 | 81 | 7 | 33 | 52 | 1 | 120 | 70 | <0.001 | 3.39 | (1.96–7.71) |
Monocytes > 0.62 (×103/mm3) b | 74 | 68 | 6 | 27 | 44 | 5 | 101 | 59 | <0.001 | 3.26 | (1.70–6.26) |
Thrombocytes > 307.5 (×103/mm3) b | 87 | 77 | 1 | 32 | 49 | 1 | 119 | 66 | <0.001 | 3.42 | (1.79–6.54) |
Uric acid > 0.225 mg/dL d | 75 | 75 | 15 | 33 | 58 | 10 | 108 | 69 | 0.03 | 2.18 | (1.09–4.37) |
LD > 260.0 U/L b, f | 19 | 79 | 7 | 29 | 47 | 5 | 48 | 56 | 0.01 | 3.68 | (1.23–11.03) |
CRP > 3.35 µg/mL e | 78 | 82 | 20 | 20 | 36 | 11 | 98 | 65 | <0.001 | 8.26 | (3.87–17.62) |
TARC > 850.0 pg/mL g | 69 | 90 | 7 | 3 | 8 | 30 | 72 | 63 | <0.001 | 97.75 | (24.37–392.06) |
Presence of B-symptoms | |||||||||||
Presence of ≥1 B-symptoms | 41 | 36 | 1 | 19 | 31 | 5 | 60 | 34 | 0.51 | 1.27 | (0.66–2.46) |
Weight loss | 17 | 15 | 3 | 11 | 19 | 8 | 28 | 16 | 0.66 | 0.78 | (0.34–1.79) |
Night sweats | 28 | 26 | 5 | 10 | 17 | 8 | 38 | 23 | 0.25 | 1.67 | (0.74–3.74) |
Fever | 18 | 16 | 3 | 11 | 17 | 2 | 29 | 16 | 1.00 | 0.94 | (0.41–2.14) |
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Zijtregtop, E.A.M.; Winterswijk, L.A.; Beishuizen, T.P.A.; Zwaan, C.M.; Nievelstein, R.A.J.; Meyer-Wentrup, F.A.G.; Beishuizen, A. Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma. Cancers 2023, 15, 1178. https://doi.org/10.3390/cancers15041178
Zijtregtop EAM, Winterswijk LA, Beishuizen TPA, Zwaan CM, Nievelstein RAJ, Meyer-Wentrup FAG, Beishuizen A. Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma. Cancers. 2023; 15(4):1178. https://doi.org/10.3390/cancers15041178
Chicago/Turabian StyleZijtregtop, Eline A. M., Louise A. Winterswijk, Tammo P. A. Beishuizen, Christian M. Zwaan, Rutger A. J. Nievelstein, Friederike A. G. Meyer-Wentrup, and Auke Beishuizen. 2023. "Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma" Cancers 15, no. 4: 1178. https://doi.org/10.3390/cancers15041178