Development and validation of novel nomograms to predict survival of patients with tongue squamous cell carcinoma

Table 1 Clinicopathological characteristics of patients with tongue squamous cell carcinoma

Variables	Training cohort (n = 3454)	Validation cohort (n = 203)
	Cases (%)	Cases (%)
Age1(yr)
< 50	685 (19.8)	42 (20.7)
≥ 50, < 60	1049 (30.4)	65 (32.0)
≥ 60, < 70	976 (28.3)	54 (26.6)
≥ 70	744 (21.5)	42 (20.7)
Sex
Male	2218 (64.2)	121(59.6)
Female	1236 (35.8)	82 (40.4)
Marital status
Married	2098 (60.7)	179 (88.2)
Unmarried2	1356 (39.3)	24 (11.8)
Race
White	2978 (86.2)	0
Black	175 (5.1)	0
Other3	301 (8.7)	203 (100)
Site
Anterior 2/3 of tongue4	2577 (74.6)	167 (82.3)
Base of tongue	877 (25.4)	36 (17.7)
T stage
T1	1720 (49.8)	88 (43.3)
T2	1095 (31.7)	98 (48.3)
T3	348 (10.1)	12 (5.9)
T4	291 (8.4)	5 (2.5)
N stage
N0	1920 (55.6)	133 (65.5)
N1	513 (14.9)	24 (11.8)
N2	973 (28.2)	45 (22.2)
N3	48 (1.4)	1 (0.5)
TNM stage
I	1237 (35.8)	65 (32.0)
II	516 (14.9)	59 (29.1)
III	565 (16.4)	31 (15.3)
IV	1136 (32.9)	48 (23.6)
Pathology grade
Well differentiated	722 (20.9)	141 (69.5)
Moderately differentiated	1787 (51.7)	56 (27.6)
Poorly differentiated	945 (27.4)	6 (3.0)
Neck dissection
No	963 (27.9)	9 (4.4)
Yes	2491 (72.1)	194 (95.6)
Radiation
No radiation	1701 (49.2)	107 (52.7)
Radiation prior to surgery	43 (1.2)	4 (2.0)
Radiation after surgery	1698 (49.2)	73 (36.0)
Radiation before and after surgery	12 (0.3)	19 (9.4)

¹Age at diagnosis.

²Unmarried, including divorced, separated, sigle, and widowed.

³Other, including American Indian/AK Native and Asian/Pacific Islander.

⁴Anterior 2/3 of the tongue refers to all parts of the tongue except for the base of the tongue and includes the border, ventral surface, dorsal surface, and overlapping lesions of the tongue.

HR: Hazard ratio; CI: Confidence interval; OS: Overall survival; TNM: Tumor-node-metastasis.

Table 2 Univariate and multivariate analyses of variables associated with overall survival

Variables	OS
	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age1 (yr)
< 50	1.0		1.0
≥ 50, < 60	1.002 (0.821, 1.223)	0.984	0.982 (0.803, 1.201)	0.858
≥ 60, < 70	1.181 (0.971, 1.438)	0.097	1.276 (1.045, 1.559)	0.017
≥ 70	1.800 (1.482, 2.187)	< 0.001	2.217 (1.815, 2.710)	< 0.001
Sex
Male	1.0		1.0
Female	0.983 (0.859, 1.124)	0.801	0.901 (0.783, 1.037)	0.147
Marital status
Married	1.0		1.0
Unmarried2	1.606 (1.413, 1.827)	< 0.001	1.388 (1.216, 1.585)	< 0.001
Race
White	1.0		1.0
Black	1.649 (1.296, 2.100)	< 0.001	1.199 (0.935, 1.538)	0.153
Other3	1.077 (0.857, 1.354)	0.526	1.102 (0.874, 1.390)	0.411
Site
Anterior 2/3 of tongue4	1.0		1.0
Base of tongue	0.757 (0.647, 0.886)	< 0.001	0.413 (0.342, 0.497)	< 0.001
T stage
T1	1.0		1.0
T2	2.168 (1.847, 2.544)	< 0.001	1.969 (1.540, 2.518)	< 0.001
T3	3.997 (3.293, 4.852)	< 0.001	3.142 (2.411, 4.095)	< 0.001
T4	5.070 (4.171, 6.163)	< 0.001	4.682 (3.498, 6.268)	< 0.001
N stage
N0	1.0		1.0
N1	2.066 (1.725, 2.475)	< 0.001	2.080 (1.497, 2.889)	< 0.001
N2	2.489 (2.154, 2.878)	< 0.001	3.749 (2.554, 5.503)	< 0.001
N3	3.040 (1.995, 4.634)	< 0.001	5.641 (3.223, 9.873)	< 0.001
TNM stage
I	1.0		1.0
II	1.831 (1.459, 2.299)	< 0.001	1.011 (0.719, 1.420)	0.952
III	2.617 (2.129, 3.216)	< 0.001	1.071 (0.709, 1.619)	0.745
IV	3.439 (2.890, 4.092)	< 0.001	0.774 (0.475, 1.262)	0.305
Pathology grade
Well differentiated	1.0		1.0
Moderately differentiated	2.141 (1.748, 2.622)	< 0.001	1.781 (1.442, 2.200)	< 0.001
Poorly differentiated	2.045 (1.642, 2.546)	< 0.001	1.733 (1.360, 2.209)	< 0.001
Neck dissection
No	1.0		1.0
Yes	1.407 (1.209, 1.638)	< 0.001	0.766 (0.640, 0.916)	0.004
Radiation
No radiation	1.0		1.0
Radiation prior to surgery	3.235 (2.156, 4.854)	< 0.001	1.345 (0.870, 2.080)	0.182
Radiation after surgery	1.629 (1.425, 1.861)	< 0.001	0.716 (0.5994, 0.856)	< 0.001
Radiation before and after surgery	3.111 (1.472, 6.575)	0.003	1.025 (0.475, 2.212)	0.0.949

¹Age at diagnosis.

²Unmarried, including divorced, separated, single, and widowed.

³Other, including American Indian/AK Native and Asian/Pacific Islander.

⁴Anterior 2/3 of the tongue refers to all parts of the tongue except for the base of the tongue and includes the border, ventral surface, dorsal surface, and overlapping lesions of the tongue.

HR: Hazard ratio; CI: Confidence interval; OS: Overall survival; TNM: Tumor-node-metastasis.

Table 3 Univariate and multivariate analyses of variables associated with cancer-specific survival

Variables	CSS
	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age1 (yr)
< 50	1.0		1.0
≥ 50, < 60	0.940 (0.760, 1.164)	0.571	0.910 (0.734, 1.129)	0.390
≥ 60, < 70	1.093 (0.885, 1.350)	0.408	1.180 (0.952, 1.463)	0.131
≥ 70	1.359 (1.094, 1.689)	0.006	1.750 (1.399, 2.189)	< 0.001
Sex
Male	1.0		1.0
Female	1.021 (0.879, 1.185)	0.786	0.999 (0.854, 1.167)	0.986
Marital status
Married	1.0		1.0
Unmarried2	1.515 (1.312, 1.749)	< 0.001	1.291 (1.114, 1.497)	< 0.001
Race
White	1.0		1.0
Black	1.739 (1.337, 2.262)	< 0.001	1.213 (0.925, 1.590)	0.163
Other3	1.079 (0.836, 1.394)	0.558	1.113 (0.0.859, 1.442)	0.420
Site
Anterior 2/3 of tongue4	1.0		1.0
Base of tongue	0.795 (0.669, 0.945)	0.009	0.393 (0.320, 0.482)	< 0.001
T stage
T1	1.0		1.0
T2	2.397 (1.994, 2.880)	< 0.001	1.973 (1.520, 2.561)	< 0.001
T3	4.832 (3.898, 5.991)	< 0.001	3.220 (2.429, 4.268)	< 0.001
T4	5.933 (4.771, 7.377)	< 0.001	4.786 (3.519, 6.510)	< 0.001
N stage
N0	1.0		1.0
N1	2.756 (2.250, 3.375)	< 0.001	2.376 (1.635, 3.454)	< 0.001
N2	3.401 (2.880, 4.016)	< 0.001	5.216 (3.337, 8.154)	< 0.001
N3	4.400 (2.843, 6.810)	< 0.001	8.289 (4.498, 15.275)	< 0.001
TNM stage
I	1.0		1.0
II	1.865 (1.405, 2.475)	< 0.001	1.019 (0.689, 1.507)	0.926
III	3.597 (2.829, 4.572)	< 0.001	1.226 (0.766, 1.964)	0.396
IV	4.720 (3.830, 5.816)	< 0.001	0.710 (0.404, 1.247)	0.233
Pathology grade
Well differentiated	1.0		1.0
Moderately differentiated	2.586 (2.024, 3.304)	< 0.001	2.895 (1.469, 2.444)	< 0.001
Poorly differentiated	2.632 (2.030, 3.414)	< 0.001	1.911 (1.438, 2.540)	< 0.001
Neck dissection
No	1.0		1.0
Yes	1.710 (1.429, 2.047)	< 0.001	0.775 (0.628, 0.957)	0.018
Radiation
No radiation	1.0		1.0
Radiation prior to surgery	4.294 (2.800, 6.586)	< 0.001	1.511 (0.952, 2.399)	0.080
Radiation after surgery	2.079 (1.782, 2.426)	< 0.001	0.769 (0.628, 0.943)	0.012
Radiation before and after surgery	4.478 (2.112, 9.495)	< 0.001	1.271 (0.585, 2.760)	0.545

¹Age at diagnosis.

²Unmarried, including divorced, separated, single, and widowed.

³Other, including American Indian/AK Native and Asian/Pacific Islander.

⁴Anterior 2/3 of the tongue refers to all parts of the tongue except for the base of the tongue and includes the border, ventral surface, dorsal surface, and overlapping lesions of the tongue.

CSS: Cancer-specific survival; CI: Confidence interval; HR: Hazard ratio; TNM: Tumor-node-metastasis.

Table 4 Net reclassification index and concordance index values of the nomograms and tumor-node-metastasis staging system, reflecting the predictive accuracy for overall and cancer-specific survival in tongue squamous cell carcinoma patients

Index	Training cohort		Validation cohort
	Estimate	95%CI	Estimate	95%CI
NRI (vs TNM stage)
For 3-year OS	0.493	(0.418, 0.589)	0.635	(0.228, 1.096)
For 5-year OS	0.482	(0.413, 0.613)	0.750	(0.397, 1.240)
For 3-year CSS	0.424	(0.354, 0.523)	0.354	(0.145, 1.037)
For 5-year CSS	0.402	(0.345, 0.536)	0.608	(0.180, 1.186)
C-index
The nomogram OS	0.741	(0.725, 0.756)	0.800	(0.747, 0.853)
The nomogram CSS	0.757	(0.739, 0.775)	0.830	(0.779, 0.881)
TNM stage OS	0.643	(0.636, 0.668)	0.695	(0.617, 0.750)
TNM stage CSS	0.678	(0.660, 0.696)	0.749	(0.673, 0.825)

CI: Confidence interval; NRI: Net reclassification index; C-index: Concordance index; OS: Overall survival; CSS: Cancer-specific survival; TNM: Tumor-node-metastasis.