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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (1): 120-130. doi: 10.19723/j.issn.1671-167X.2024.01.019

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Establishment and verification of a prognostic nomogram for survival of tongue squamous cell carcinoma patients who underwent cervical dissection

Junqi SU1,Xiaoying WANG2,Zhiqiang SUN1,*()   

  1. 1. Department of Clinical Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
    2. Department of Medical Record, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
  • Received:2023-08-30 Online:2024-02-18 Published:2024-02-06
  • Contact: Zhiqiang SUN E-mail:sunzhiqiang963@163.com

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Abstract:

Objective: To evaluate the prognostic significance of inflammatory biomarkers, prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma (TSCC) patients who underwent cervical dissection. Methods: The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018. The study population was divided into the training set and validation set by 7 :3 randomly. The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation score (SIS) and prognostic nutritional index (PNI). Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). The nomogram's accuracy was internally validated using concordance index, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration plot and decision curve analysis. Results: According to the univariate Cox regression analysis, clinical TNM stage, clinical T category, clinical N category, differentiation grade, depth of invasion (DOI), tumor size and pre-treatment PNI were the prognostic factors of TSCC. Multivariate Cox regression analysis revealed that pre-treatment PNI, clinical N category, DOI and tumor size were independent prognostic factors for OS or DSS (P < 0.05). Positive neck nodal status (N≥1), PNI≤50.65 and DOI > 2.4 cm were associated with the poorer 5-year OS, while a positive neck nodal status (N≥1), PNI≤50.65 and tumor size > 3.4 cm were associated with poorer 5-year DSS. The concordance index of the nomograms based on independent prognostic factors was 0.708 (95%CI, 0.625-0.791) for OS and 0.717 (95%CI, 0.600-0.834) for DSS. The C-indexes for external validation of OS and DSS were 0.659 (95%CI, 0.550-0.767) and 0.780 (95%CI, 0.669-0.890), respectively. The 1-, 3- and 5-year time-dependent ROC analyses (AUC = 0.66, 0.71 and 0.72, and AUC = 0.68, 0.77 and 0.79, respectively) of the nomogram for the OS and DSS pronounced robust discriminative ability of the model. The calibration curves showed good agreement between the predicted and actual observations of OS and DSS, while the decision curve confirmed its pronounced application value. Conclusion: Pre-treatment PNI, clinical N category, DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC. The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection. They are effective tools for predicting survival and helps to choose appropriate treatment strategies to improve the prognosis.

Key words: Tongue squamous cell carcinoma, Prognostic nutritional index, Prognostic prediction model, Overall survival, Disease-specific survival, Nomogram

CLC Number: 

  • R739.8

Table 1

Demographic and clinicopathological characteristics of patients with TSCC"

Characteristics Total
(n=297)		 Training cohort
(n=208)		 Validation cohort
(n=89)		 P value
Age /years
  ≤60 200 (67.34) 147 (70.67) 53 (59.55) 0.061
  ＞60 97 (32.66) 61 (29.33) 36 (40.45)
Gender
  Male 179 (60.27) 128 (61.54) 51 (57.30) 0.494
  Female 118 (39.73) 80 (38.46) 38 (42.70)
Alcohol consumption
  Current 85 (28.62) 58 (27.88) 27 (30.34) 0.668
  Former or never 212 (71.38) 150 (72.12) 62 (69.66)
Smoking
  Current 114 (38.38) 78 (37.50) 36 (40.45) 0.632
  Former or never 183 (61.62) 130 (62.50) 53 (59.55)
Clinical TNM stage
  Ⅰ-Ⅱ 203 (68.35) 145 (69.71) 58 (65.17) 0.441
  Ⅲ-Ⅳ 94 (31.65) 63 (30.29) 31 (34.83)
Clinical T category
  T1-T2 247 (83.16) 175 (84.13) 72 (80.90) 0.495
  T3-T4 50 (16.84) 33 (15.87) 17 (19.10)
Clinical N category
  N0 219 (73.74) 153 (73.56) 66 (74.16) 0.914
  N+ 78 (26.26) 55 (26.44) 23 (25.84)
Differentiation grade
  Well 82 (27.61) 61 (29.33) 21 (23.60) 0.311
  Moderate/poor 215 (72.39) 147 (70.67) 68 (76.40)
Depth of invasion
  ≤2.4 cm 248 (83.50) 174 (83.65) 74 (83.15) 0.914
  ＞2.4 cm 49 (16.50) 34 (16.35) 15 (16.85)
Tumor size
  ≤3.4 cm 235 (79.12) 165 (79.33) 70 (78.65) 0.896
  ＞3.4 cm 62 (20.88) 43 (20.67) 19 (21.35)
NLR
  ≤1.26 53 (17.85) 38 (18.27) 15 (16.85) 0.77
  ＞1.26 244 (82.15) 170 (81.73) 74 (83.15)
LMR
  ≤6.89 244 (82.15) 169 (81.25) 75 (84.27) 0.534
  ＞6.89 53 (17.85) 39 (18.75) 14 (15.73)
PLR
  ≤138.67 198 (66.67) 143 (68.75) 55 (61.80) 0.244
  ＞138.67 99 (33.33) 65 (31.25) 34 (38.20)
SII
  ≤301.54 76 (25.59) 50 (24.04) 26 (29.21) 0.349
  ＞301.54 221 (74.41) 158 (75.96) 63 (70.79)
PNI
  ≤50.65 113 (38.05) 73 (35.10) 40 (44.94) 0.109
  ＞50.65 184 (61.95) 135 (64.90) 49 (55.06)
SIS
  0 153 (51.52) 110 (52.88) 43 (48.31) 0.327
  1 114 (38.38) 80 (38.46) 34 (38.20)
  2 30 (10.10) 18 (8.65) 12 (13.48)

Table 2

Evaluation of immune-inflammation index and prognostic nutritional index of patients with TSCC"

Parameters Values, ${\bar x}$±s
White blood cell count
  Neutrophil/(×109/L) 3.76±1.34
  Lymphocyte/(×109/L) 1.98±0.63
  Monocyte/(×109/L) 0.40±0.14
  Platelet/(×109/L) 238.03±62.57
  Alb/(g/L) 42.42±3.45
Calculated ratios
  NLR 2.08±1.03
  LMR 5.39±2.12
  PLR 131.07±53.28
  SII 499.00±300.82
  PNI 52.33±4.99

Table 3

Cox regression for overall survival of patients with TSCC"

Variables Patients, n(%) Events, n(%) Univariate analysis Multivariate analysis
HR 95%CI P value HR 95%CI P value
Gender
  Male 179 (60.27) 33 (60.00) 1 (ref.)
  Female 118 (39.73) 22 (40.00) 0.979 0.571-1.679 0.938
Age /years
  ≤60 200 (67.34) 36 (65.45) 1 (ref.)
  ＞60 97 (32.66) 19 (34.55) 1.074 0.616-1.872 0.801
Alcohol consumption
  Current 85 (28.62) 19 (34.55) 1 (ref.)
  Former or never 212 (71.38) 36 (65.45) 0.702 0.403-1.224 0.212
Smoking
  Current 114 (38.38) 22 (40.00) 1 (ref.)
  Former or never 183 (61.62) 33 (60.00) 0.905 0.528-1.552 0.716
Clinical TNM stage
  Ⅰ-Ⅱ 203 (68.35) 31 (56.36) 1 (ref.)
  Ⅲ-Ⅳ 94 (31.65) 24 (43.64) 1.911 1.121-3.258 0.017* 0.442
Clinical T category
  T1-T2 247 (83.16) 42 (76.36) 1 (ref.)
  T3-T4 50 (16.84) 13 (23.64) 1.701 0.913-3.170 0.094 0.962
Clinical N category
  N0 219 (73.74) 31 (56.36) 1 (ref.) 1 (ref.)
  N+ 78 (26.26) 24 (43.64) 2.659 1.559-4.534 0.000* 2.277 1.319-3.930 0.003*
Differentiation grade
  Well 82 (27.61) 9 (16.36) 1 (ref.)
  Moderate/poor 215 (72.39) 46 (83.64) 2.156 1.055-4.405 0.035* 0.080
Depth of invasion
  ≤2.4 cm 248 (83.50) 38 (69.09) 1 (ref.) 1 (ref.)
  ＞2.4 cm 49 (16.50) 17 (30.91) 2.547 1.437-4.512 0.001* 1.829 1.013-3.302 0.045*
Tumor size
  ≤3.4 cm 235 (79.12) 35 (63.64) 1 (ref.)
  ＞3.4 cm 62 (20.88) 20 (36.36) 2.334 1.347-4.044 0.003* 0.410
NLR
  ≤1.26 53 (17.85) 14 (25.45) 1 (ref.)
  ＞1.26 244 (82.15) 41 (74.55) 0.593 0.323-1.088 0.092 0.110
LMR
  ≤6.89 244 (82.15) 50 (90.91) 1 (ref.)
  ＞6.89 53 (17.85) 5 (9.09) 0.420 0.168-1.054 0.065 0.192
PLR
  ≤138.67 198 (66.67) 40 (72.73) 1 (ref.)
  ＞138.67 99 (33.33) 15 (27.27) 0.760 0.420-1.375 0.364
SII
  ≤301.54 76 (25.59) 18 (32.73) 1 (ref.)
  ＞301.54 221 (74.41) 37 (67.27) 0.668 0.380-1.174 0.161
PNI
  ≤50.65 113 (38.05) 31 (56.36) 1 (ref.) 1 (ref.)
  ＞50.65 184 (61.95) 24 (43.64) 0.409 0.240-0.698 0.001* 0.462 0.269-0.793 0.005*
SIS
  0 153 (51.51) 27 (49.09) 1 (ref.)
  1 114 (38.38) 22 (40.00) 1.103 0.628-1.936 0.734
  2 30 (10.10) 6 (10.91) 1.101 0.455-2.667 0.831

Figure 1

Kaplan-Meier survival curves for OS in relation to clinical N category (A), pre-treatment PNI (B) and DOI (C) OS, overall survival; PNI, prognostic nutritional index; DOI, depth of invasion; HR, hazard ratio; CI, confidence interval."

Table 4

Cox regression for disease-specific survival of patients with TSCC"

Variables Patients, n(%) Events, n(%) Univariate analysis Multivariate analysis
HR 95%CI P value HR 95%CI P value
Gender
  Male 179 (60.27) 23 (67.65) 1 (ref.)
  Female 118 (39.73) 11 (32.35) 0.704 0.343-1.443 0.338
Age /years
  ≤60 200 (67.34) 23 (67.65) 1 (ref.)
  ＞60 97 (32.66) 11 (32.35) 0.976 0.476-2.001 0.946
Alcohol consumption
  Current 85 (28.62) 13 (38.24) 1 (ref.)
  Former or never 212 (71.38) 21 (61.76) 0.603 0.302-1.204 0.151
Smoking
  Current 114 (38.38) 16 (47.06) 1 (ref.)
  Former or never 183 (61.62) 18 (52.94) 0.681 0.347-1.335 0.263
Clinical TNM stage
  Ⅰ-Ⅱ 203 (68.35) 17 (50.00) 1 (ref.)
  Ⅲ-Ⅳ 94 (31.65) 17 (50.00) 2.414 1.232-4.731 ＜0.001* 0.300
Clinical T category
  T1-T2 247 (83.16) 24 (70.59) 1 (ref.)
  T3-T4 50 (16.84) 10 (29.41) 2.249 1.075-4.705 0.031* 0.744
Clinical N category
  N0 219 (73.74) 16 (47.06) 1 (ref.) 1 (ref.)
  N+ 78 (26.26) 18 (52.94) 3.744 1.908-7.348 ＜0.001* 2.783 1.373-5.640 0.005*
Differentiation grade
  Well 82 (27.61) 6 (17.65) 1 (ref.)
  Moderate/poor 215 (72.39) 28 (82.35) 1.936 0.801-4.676 0.142
Depth of invasion
  ≤2.4 cm 248 (83.50) 21 (61.76) 1 (ref.)
  ＞2.4 cm 49 (16.50) 13 (38.24) 3.463 1.734-6.916 ＜0.001* 0.278
Tumor size
  ≤3.4 cm 235 (79.12) 18 (52.94) 1 (ref.) 1 (ref.)
  ＞3.4 cm 62 (20.88) 16 (47.06) 3.530 1.800-6.925 ＜0.001* 2.336 1.148-4.751 0.019*
NLR
  ≤1.26 53 (17.85) 8 (23.53) 1 (ref.)
  ＞1.26 244 (82.15) 26 (76.47) 0.672 0.304-1.485 0.326
LMR
  ≤6.89 244 (82.15) 32 (94.12) 1 (ref.)
  ＞6.89 53 (17.85) 2 (5.88) 0.266 0.064-1.109 0.069 0.188
PLR
  ≤138.67 198 (66.67) 24 (70.59) 1 (ref.)
  ＞138.67 99 (33.33) 10 (29.41) 0.852 0.407-1.782 0.671
SII
  ≤301.54 76 (25.59) 10 (29.41) 1 (ref.)
  ＞301.54 221 (74.41) 24 (70.59) 0.798 0.382-1.670 0.550
PNI
  ≤50.65 113 (38.05) 21 (61.76) 1 (ref.) 1 (ref.)
  ＞50.65 184 (61.95) 13 (38.24) 0.335 0.168-0.670 0.002* 0.403 0.200-0.812 0.011*
SIS
  0 153 (51.51) 16 (47.06) 1 (ref.)
  1 114 (38.38) 13 (38.24) 1.104 0.531-2.295 0.791
  2 30 (10.10) 5 (14.70) 1.535 0.562-4.189 0.403

Figure 2

Kaplan-Meier survival curves for DSS in relation to clinical N category (A), pre-treatment PNI (B) and tumor size (C) DSS, disease-specific survival; PNI, prognostic nutritional index; HR, hazard ratio; CI, confidence interval."

Figure 3

Nomograms predicting 1-, 3- and 5-year probalilities for OS (A) and DSS (B) in patients with TSCC TSCC, tongue squamous cell carcinoma; OS, overall survival; DSS, disease-specific survival."

Figure 4

ROC analysis of nomogram for the OS and DSS in patients with TSCC A, time-dependent ROC curve for 1-, 3-, 5-year OS; B, time-dependent ROC curve for 1-, 3-, 5-year DSS. TSCC, tongue squamous cell carcinoma; OS, overall survival; DSS, disease-specific survival; ROC, receiver operating characteristic; AUC, area under the curve."

Figure 5

Nomogram model calibration curves for 5-year prediction for OS and DSS in patients with TSCC in training cohort and validation cohort A, 5-year for OS in the training set; B, 5-year for OS in the validation set; C, 5-year for DSS in the training set; D, 5-year for DSS in the validation set. TSCC, tongue squamous cell carcinoma; OS, overall survival; DSS, disease-specific survival."

Figure 6

Nomogram model decision curves for 5-year prediction for OS and DSS in patients with TSCC in training cohort and validation cohort A, 5-year for OS in the training set; B, 5-year for OS in the validation set; C, 5-year for DSS in the training set; D, 5-year for DSS in the validation set. TSCC, tongue squamous cell carcinoma; OS, overall survival; DSS, disease-specific survival."

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