New prognostic model for patients with advanced gastric cancer: Fluoropyrimidine/platinum doublet for first-line chemotherapy

Table 1 Patient characteristics during first-line doublet chemotherapy according to treatment period

Clinical characteristics	Training set (2012-2015), n = 937	Validation set (2008-2011), n = 946	P value
Sex, male, n (%)	583 (62.2)	637 (67.3)	0.020
Age
Median, range	56 (19-91)	57 (20-85)	0.785
≥ 65 yr, n (%)	257 (27.4)	259 (27.4)	0.981
ECOG PS, n (%)
0/1	799 (85.6)	817 (86.6)	0.531
2/3	134 (14.4)	126 (13.4)
Prior gastrectomy performed	389 (41.5)	412 (43.6)	0.372
Histology, n (%)
WD/MD	212 (22.6)	256 (27.1)	< 0.001
PD/SRC/undifferentiated	691 (73.7)	590 (62.4)
Unclassified	34 (3.6)	100 (10.6)
Status, n (%)
Recurrent	318 (33.9)	334 (35.3)	0.533
Initial metastatic	619 (66.1)	612 (64.7)
Metastasis No., 2 or more	385 (41.5)	363 (38.9)	0.249
Peritoneal metastasis	518 (55.6)	524 (55.9)	0.902
Liver metastasis	160 (17.2)	226 (24.1)	< 0.001
Lung metastasis	45 (4.9)	43 (4.6)	0.795
PALN metastasis	346 (37.3)	352 (37.5)	0.942
Bone metastasis	93 (10.0)	70 (7.5)	0.051
ALP > 120 IU/L, n (%)	201 (21.5)	197 (21.2)	0.868
Albumin < 3.3 g/dL, n (%)	279 (29.8)	249 (26.8)	0.150
Total bilirubin > 1.2 mg/dL, n (%)	62 (6.6)	77 (8.3)	0.177
NLR ≥ 3, n (%)	381 (40.7)	375 (40.3)	0.881

ECOG PS: Eastern Cooperative Oncology Group performance status; WD: Well differentiated; MD: Moderately differentiated; PD: Poorly differentiated; SRC: Signet ring cell; PALN: Para-aortic lymph node; ALP: Alkaline phosphatase; NLR: Neutrophil-lymphocyte ratio.

Table 2 Comparison between the old model and new model developed from the training set

Factors	Old model	Univariate analysis		Multivariate analysis		New model
	Score	HR	P value	HR	P value	Score
Poor PS	2	1.983	< 0.001	2.005	< 0.001	2
No gastrectomy	1	1.046	0.542	-	-	-
Peritoneal metastasis	1	1.355	< 0.001	1.355	< 0.001	1
Bone metastasis	2	1.605	< 0.001	1.651	< 0.001	2
Lung metastasis	1	1.249	0.188	-	-	-
High ALP	1	1.435	< 0.001	1.406	< 0.001	1
Low albumin	1	1.410	< 0.001	1.447	< 0.001	1
High total bilirubin	1	0.965	0.806	-	-	-
High NLR	-	1.445	< 0.001	1.461	< 0.001	1
Poor histology	-	1.104	0.253	-	-	-

HR: Hazard ratio; poor PS: Performance status 2/3; high ALP: Alkaline phosphatase > 120 IU/L; low albumin: Albumin < 3.3 g/dL; high NLR: Neutrophil-lymphocyte ratio ≥ 3.

Table 3 Survival outcomes of first-line doublet regimens in the training and validation sets according to the new prognostic model

Risk group	Good risk, 0-1 point(s)	Moderate risk, 2-3 points	Poor risk, ≥ 4 points	P value
Training set (2012-2015)
No. of patients	449 (48.8%)	319 (34.7%)	152 (16.5%)
Hazard ratio (95%CI)	Reference	1.628 (1.40-1.90)	4.013 (3.30-4.88)	< 0.001
Median OS, mo (95%CI)	15.9 (14.5-17.4)	10.6 (9.3-11.9)	4.7 (4.0-5.5)	< 0.001
Median PFS, mo (95%CI)	8.3 (7.4-9.1)	5.9 (5.1-6.6)	2.4 (1.8-2.9)	< 0.001
Survival rate (%)
At 6 mo	90.0% (87.2-92.8)	74.0% (69.2-78.8)	37.5% (29.8-45.2)
At 12 mo	63.2% (58.7-67.7)	44.0% (38.6-49.4)	16.1% (10.3-21.9)
At 18 mo	42.9% (38.3-47.5)	23.4% (18.8-28.0)	6.3% (2.4-10.2)
At 24 mo	31.2% (26.9-35.5)	16.4% (12.3-20.5)	2.8% (0.2-5.4)
Validation set (2008-2011)
No. of patients	474 (52.0%)	291 (31.9%)	147 (16.1%)
Hazard ratio (95%CI)	Reference	1.634 (1.41-1.90)	2.963 (2.45-3.59)	< 0.001
Median OS, mo (95%CI)	15.8 (14.8-16.9)	10.1 (8.7-11.5)	5.7 (4.7-6.6)	< 0.001
Median PFS, mo (95%CI)	7.0 (6.3-7.7)	5.6 (5.1-6.1)	3.2 (2.5-3.9)	< 0.001
Survival rate (%)
At 6 mo	88.6% (85.7-91.5)	72.2% (67.1-77.3)	47.6% (39.6-55.7)
At 12 mo	64.3% (60.0-68.6)	42.3% (36.6-48.0)	17.0% (10.9-23.1)
At 18 mo	40.1% (35.7-44.5)	22.0% (17.2-26.8)	6.1% (2.2-10.0)
At 24 mo	25.9% (22.0-29.8)	13.1% (9.2-17.0)	4.8% (1.3-8.3)
Validation set (2008-2011) according to old model
No. of patients	393 (41.7%)	390 (41.4%)	160 (16.9%)
Hazard ratio (95%CI)	Reference	1.493 (1.29-1.73)	3.281 (2.71-3.98)	< 0.001
Median OS, mo (95%CI)	16.2 (15.3-17.1)	10.7 (9.5-12.0)	5.5 (4.5-6.5)	< 0.001
Median PFS, mo (95%CI)	7.1 (6.3-7.9)	5.6 (5.1-6.2)	3.3 (2.5-4.0)	< 0.001
Survival rate (%)
At 6 mo	90.3% (87.4-93.2)	75.8% (71.5-80.1)	47.5% (39.8-55.2)
At 12 mo	68.2% (63.6-72.8)	45.5% (40.6-50.4)	16.3% (10.6-22.0)
At 18 mo	41.3% (36.4-46.2)	26.5% (22.1-30.9)	5.6% (2.0-9.2)
At 24 mo	27.4% (23.0-31.8)	17.0% (13.3-20.7)	3.1% (0.4-5.8)

OS: Overall survival; PFS: Progression-free survival; CI: Confidence interval.