Value of Nomogram Incorporated Preoperative Tumor Volume and the Number of Postoperative Pathologically Lymph Node Metastasis Regions on Predicting the Prognosis of Thoracic Esophageal Squamous Cell Carcinoma

Figures & data

Table 1 Clinicopathological Characteristics of 296 Patients with Esophageal Squamous Cell Carcinoma Receiving Surgery

Characteristics	Patients, n (%)
Sex
Male	239 (80.7)
Female	57 (19.3)
Age (years)
<63	140 (47.3)
≥63	156 (52.7)
Tumor location
Upper 1/3	13 (4.4)
Middle 1/3	184 (62.2)
Lower 1/3	99 (33.4)
Differential grade
Well	20 (6.8)
Moderately	220 (74.3)
Poor	56 (18.9)
T stage
T1	22 (7.4)
T2	102 (34.5)
T3	164 (55.4)
T4	8 (2.7)
N stage
N0	146 (49.3)
N1	93 (31.4)
N2	45 (15.2)
N3	12 (4.1)
TNM stage
I	17 (5.7)
II	132 (44.6)
III	147 (49.7)
Adjuvant therapy
No	127 (42.9)
Yes	169 (57.1)
Preoperative tumor volume (cm^3)
<28	86 (29.1)
28–64	108 (36.5)
>64	102 (34.4)
Preoperative length (cm)
<3.0	62 (20.9)
3.0–5.0	146 (49.3)
>5.0	88 (29.8)
Preoperative maximum diameter (cm)
<2.5	51 (17.2)
2.5–3.5	121 (40.9)
>3.5	124 (41.9)
The number of LNM regions
Non-regional LNM	147 (49.7)
Oligo-regional LNM	95 (32.1)
Multi-regional LNM	54 (18.2)

Figure 1 Kaplan–Meier survival curves for progression-free survival (PFS) in patients with ESCC receiving surgery. (A) 1-, 3-, and 5-year PFS of patients with preoperative tumor volume <28 cm³ were longer than those with 28–64 cm³ group or >64 cm³ group. (P< 0.001, log-rank). (B) 1-, 3-, and 5-year PFS of patients with preoperative tumor length <3 cm were obvious different from those with 3–5 cm group or >5 cm group. (P < 0.001, log-rank). (C) 1-, 3-, and 5-year PFS of patients with preoperative maximum diameter <2.5 cm group were obviously improved compared with patients of 2.5–3.5 cm group or >3.5 cm group. (P < 0.001, log-rank). (D) 1-, 3-, and 5-year PFS of patients with non-regional lymph node metastasis group were longer than those with oligo or multiple-regional lymph node metastasis group. (P< 0.001, log-rank).

Figure 2 Kaplan–Meier survival curves for overall survival (OS) in patients with ESCC after surgery. (A) 1-, 3-, and 5-year OS of patients with preoperative tumor volume <32 cm³ were longer than those with 32–72 cm³ group or >72 cm³ group. (P< 0.001, log-rank). (B) 1-, 3-, and 5-year OS of patients with preoperative tumor length <3 cm were obvious different from those with 3–5 cm group or >5 cm group. (P < 0.001, log-rank). (C) 1-, 3-, and 5-year OS of patients with preoperative maximum diameter <2.5 cm group were obviously improved compared with patients of 2.5–3.5 cm group or >3.5 cm group. (P < 0.001, log-rank). (D) 1-, 3-, and 5-year OS of patients with non-regional lymph node metastasis group were longer than those with oligo or multiple-regional lymph node metastasis group. (P< 0.001, log-rank).

Table 2 Univariate and Multivariate Analysis for PFS in 296 Esophageal Squamous Cell Carcinoma Treated by Surgery

Factors	Univariate			Multivariate
	HR	95% CI	P value	HR	95% CI	P value
Age (≥63 versus <63)	1.163	0.896–1.511	0.257	–	–	–
Sex (male versus female)	1.074	0.770–1.496	0.675	–	–	–
Tumor location (upper + middle versus lower)	1.193	0.954–1.492	0.122	–	–	–
Differential grade Well + moderate versus Poor)	0.709	0.515–0.975	0.034	0.738	0.554–0.984	0.038
T stage (T3+T4 versus T1+T2)	1.441	1.103–1.883	0.007	–	–	–
N stage (N1+N2+N3 versus N0)	1.550	1.193–2.014	0.001	–	–	–
TNM stage (III+IV versus I+II)	1.544	1.189–2.005	0.001	1.219	1.138–2.218	0.012
Adjuvant therapy (Yes versus No)	0.596	0.459–0.774	<0.001	0.473	0.361–0.619	0.001
Preoperative tumor volume (cm^3)			<0.001			0.045
<28	1	–	–	1	–	–
28–64	2.625	1.828–3.772	<0.001	2.716	1.852–3.984	0.023
>64	4.061	2.828–5.832	<0.001	3.535	2.397–5.214	<0.001
Preoperative length (cm)			<0.001			0.690
<3.0	1	–	–	1	–	–
3.0–5.0	2.320	1.572–3.425	<0.001	1.016	0.588–1.755	0.954
>5.0	3.906	2.592–5.888	<0.001	1.208	0.624–2.338	0.575
Preoperative maximum diameter (cm)			<0.001			0.119
<2.5	1	–	–	1	–	–
2.5–3.5	2.506	1.585–3.963	<0.001	1.529	0.838–2.788	0.166
>3.5	4.494	2.854–7.077	<0.001	2.080	1.013–4.273	0.046
The number of LNM regions			<0.001			0.036
Non-regional LNM	1	–	–	1	–	–
Oligo-regional LNM	1.153	0.852–1.559	0.356	0.682	0.167–2.788	0.594
Multi-regional LNM	2.881	2.056–4.038	<0.001	2.576	1.387–6.428	0.021

Table 3 Univariate and Multivariate Analysis for OS in 296 Esophageal Squamous Cell Carcinoma Followed by Surgery

Factors	Univariate			Multivariate
	HR	95% CI	P value	HR	95% CI	P value
Age (≥63 versus <63)	1.296	0.978–1.717	0.071	–	–	–
Sex (male versus female)	1.247	0.861–1.804	0.243	–	–	–
Tumor location (upper + middle versus lower)	1.303	1.031–1.647	0.037	1.011	0.867–1.998	0.128
Differential grade (Well + moderate versus Poor)	0.530	0.409–0.793	0.001	0.514	0.366–0.723	0.019
T stage (T3+T4∕T1+T2)	1.915	1.423–2.577	<0.001	–	–	–
N stage (N1+N2+N3∕N0)	1.935	1.454–2.576	<0.001	–	–	–
TNM stage (III+IV/I+II)	1.876	1.412–2.493	<0.001	1.757	1.267–2.612	0.015
Adjuvant therapy (Yes versus No)	0.759	0.574–0.991	<0.001	0.669	0.503–0.889	0.006
Preoperative tumor volume (cm^3)			<0.001			<0.001
<32	1	–	–	1	–	–
32–72	3.976	2.622–6.028	<0.001	3.689	2.415–5.637	<0.001
>72	6.269	4.075–9.644	<0.001	5.720	3.606–9.075	<0.001
Preoperative tumor length (cm)			<0.001			0.677
<3.0	1	–	–	1	–	–
3.0–5.0	3.571	2.185–5.835	<0.001	1.007	0.499–2.321	0.851
>5.0	5.582	3.360–9.274	<0.001	1.234	0.634–2.404	0.536
Preoperative tumor maximum diameter (cm)			<0.001			0.373
<2.5	1	–	–	1	–	–
2.5–3.5	3.486	1.936–6.279	<0.001	1.477	0.691–3.159	0.314
>3.5	6.791	3.800–12.125	<0.001	1.755	0.763–4.128	0.183
The number of LNM regions			<0.001			0.011
Non-regional LNM	1	–	–	1	–	–
Oligo-regional LNM	1.384	1.002–2.924	0.018	1.166	1.002–2.289	0.045
Multi-regional LNM	3.573	2.501–5.104	<0.001	2.316	1.073–4.997	0.032

Figure 3 ROC curve for survival prediction. (A) ROC curves of preoperative tumor volume and the number of postoperative pathologically LNM regions for predicting PFS. (B) ROC curves of preoperative tumor volume and the number of postoperative pathologically LNM regions for predicting OS.

Figure 4 Prediction Nomogram for PFS. (A) The model that incorporated differentiation grade, TNM stage, adjuvant therapy, preoperative tumor volume and the number of postoperative pathologically LNM regions was developed and presented as the nomogram; (B) The calibration curve of the nomogram for the 5-year PFS; (C) The decision curve analysis of the nomogram for the PFS.

Figure 5 Prediction Nomogram for OS. (A) The model that integrated all significant independent factors for OS was shown as the nomogram; (B) The calibration curve of the nomogram for the 5-year OS; (C) The decision curve analysis of the nomogram for the OS.

Figure 6 Correlations among preoperative tumor volume, length, and maximum diameter. (A) Correlation chart between preoperative tumor volume and length (regression line: Y=−39.458+19.612×X, correlation coefficient: R² =0.655, P<0.001). (B) Correlation chart between preoperative tumor volume and maximum diameter (regression line: Y= −66.700+37.334×X, correlation coefficient: R² =0.684, P<0.001). (C) Correlation chart between preoperative tumor length and maximum diameter (regression line: Y= 0.697+1.236×X, correlation coefficient: R² =0.440, P<0.001).