A clinical prognostic scoring system for resectable gastric cancer to predict survival and benefit from paclitaxel- or oxaliplatin-based adjuvant chemotherapy

Figures & data

Table 1 Baseline clinicopathological features of 579 patients

Parameter	Number of patients (%)
Age, years
Median	58
Range	18–85
<58	264 (45.6)
≥58	315 (54.4)
Sex
Male	405 (69.9)
Female	174 (30.1)
Location
Cardia/fundus	153 (26.4)
Corpus	226 (39.0)
Antrum	183 (31.6)
Whole	17 (2.9)
Size, cm
<3	141 (24.4)
3–6	305 (52.7)
7–9	95 (16.4)
>9	38 (6.6)
Borrmann type
I–III	435 (75.1)
IV	144 (24.9)
Grading
Well/moderately (G1/2)	88 (15.2)
Poorly (G3)	491 (84.8)
Depth of tumor invasion
T1	49 (8.5)
T2	80 (13.8)
T3	118 (20.4)
T4	332 (57.3)
Metastatic node number
N0 (0)	147 (25.4)
N1 (1–2)	118 (20.4)
N2 (3–6)	145 (25.0)
N3 (>6)	169 (29.2)
Metastatic lymph node ratio, %
0	147 (25.2)
1–25	170 (29.5)
26–50	118 (20.4)
51–100	144 (24.9)
Lymphovascular invasion
Negative	414 (71.5)
Positive	165 (28.5)
Perineural invasion
Negative	406 (70.1)
Positive	173 (29.9)
Seventh AJCC TNM Stage
I	76 (13.1)
II	149 (25.7)
III	354 (61.1)
Type of operation
Total gastrectomy	224 (38.7)
Subtotal gastrectomy	355 (61.3)
Resection margin
R0	414 (71.5)
R1	165 (28.5)
Pre-CEA level, ng/mL
<5	243 (42.0)
≥5	336 (58.0)
Pre-CA19-9 level, U/mL
<35	487 (84.1)
≥35	92 (15.9)
Pre-red blood cell, ×10^12/L
<4	227 (39.2)
≥4	352 (60.8)
Pre-hemoglobin, g/L
<110	252 (43.5)
≥110	327 (56.5)
Pre-white blood cell, ×10^9/L
<4	51 (8.8)
≥4	528 (91.2)
Pre-platelet, ×10^9/L
≥300	60 (10.4)
<300	519 (89.6)
ASA score
0–1	568 (98.1)
≥2	11 (1.9)
Chemotherapy regimens
Triplet	81 (14.0)
Doublet	264 (45.6)
Single	234 (40.4)

Abbreviations: AJCC, American Joint Committee on Cancer; pre-, preoperative; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; ASA, The American Society of Anesthesiologists.

Table 2 Univariate and multivariate survival analyses

Variables	Univariate analysis			Multivariate analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Age (≥58 vs <58), years	1.03	0.80–1.33	0.835	–	–	–
Sex (male vs female)	1.05	0.80–1.38	0.742	–	–	–
Location (corpus/cardia/fundus vs whole)	0.99	0.75–1.32	0.958	–	–	–
Borrmann type (IV vs I–III)	1.99	0.74–5.35	0.173	–	–	–
Grade (poorly [G3] vs well–moderately [G1/2])	1.63	1.09–2.46	0.018	–	–	–
Depth of tumor invasion (pT) (pT3/pT4 vs pT1/pT2)	3.32	2.18–5.07	<0.001	1.23	0.53–1.23	0.324
Tumor size (>6 cm vs <6 cm)	1.51	1.13–2.00	0.005	1.52	0.83–2.79	0.174
Metastatic node number (pN) (pN2/pN3 vs pN0/pN1)	2.57	1.94–3.41	<0.001	1.07	0.78–1.44	0.675
Metastatic lymph node ratio (LNR) (≥50% vs <50%)	3.02	2.30–3.96	<0.001	1.81	1.32–2.49	<0.001
Lymphovascular invasion (positive vs negative)	2.16	1.66–2.80	<0.001	1.60	1.22–2.09	0.001
Perineural invasion (positive vs negative)	1.51	1.15–1.97	0.003	0.96	0.71–1.28	0.762
TNM stage (II vs I)	2.25	1.11–4.57	0.025	2.18	1.06–4.52	0.035
TNM stage (III vs I)	5.57	2.95–10.53	<0.001	3.48	1.70–7.12	0.001
Surgical margin (R1 vs R0)	2.16	1.66–2.80	<0.001	1.57	0.99–2.06	0.121
Type of gastrectomy (total vs subtotal)	1.41	1.09–1.83	0.009	1.160	0.65–1.13	0.294
Pre-CEA level (≥5 ng/mL vs <5 ng/mL)	1.34	1.03–1.75	0.027	1.13	1.02–1.73	0.034
Pre-CA19-9 level (≥35 U/mL vs <35 U/mL)	1.84	1.35–2.49	<0.001	1.35	0.99–1.85	0.061
Pre-red blood cell (<4×10^12/L vs ≥4×10^12/L)	1.16	0.90–1.50	0.261	–	–	–
Pre-hemoglobin (<110 g/L vs ≥110 g/L)	1.81	1.40–2.34	<0.001	1.57	1.21–2.03	0.001
Pre-white blood cell (<4×10^9/L vs ≥4×10^9/L)	1.15	0.73–1.82	0.55	–	–	–
Pre-platelet (≥300×10^9/L vs <300×10^9/L)	1.10	0.85–1.42	0.464	–	–	–
ASA score (<2 vs ≥2)	1.07	0.88–1.12	0.592	–	–	–
Chemotherapy regimens (triplet vs single)	1.39	0.99–1.96	0.060	–	–	–
Chemotherapy regimens (doublet vs single)	0.82	0.61–1.09	0.173	–	–	–
Taxel-based chemotherapy (yes vs no)	0.84	0.65–1.08	0.179	–	–	–
Oxaliplatin-based chemotherapy (yes vs no)	3.15	0.44–22.48	0.252	–	–	–
FU-based chemotherapy (yes vs no)	0.84	0.64–1.09	0.189	–	–	–
Cisplatin-based chemotherapy (yes vs no)	1.58	0.89–2.83	0.121	–	–	–

Abbreviations: HR, hazard ratio; CI, confidence interval; pre-, preoperative; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; ASA score, The American Society of Anesthesiologists score; FU, fluorouracil; LNR, lymph node ratio; –, not applicable.

Figure 1 Unadjusted overall survival curves for independent factors by univariate analyses: TNM stage (A), LNR (B), LVI (C), pre-CEA (D), and pre-Hb (E). Abbreviations: pre-, preoperative; CEA, carcinoembryonic antigen; Hb, hemoglobin; CA19-9, carbohydrate antigen 19-9; LNR, lymph node ratio; LVI, lymphovascular invasion.

Table 3 Definition of score index based on the coefficient in the final Cox model

Overall survival	Score points
	0	1	2	3
UICC-TNM stage	I	–	II	III
Metastatic lymph node ratio	0%–50%	–	>50%	–
Lymphovascular invasion	Negative	–	Positive	–
Pre-CEA level, ng/mL	<5	≥5	–	–
Pre-hemoglobin, g/L	≥110	–	<110	–

Abbreviations: UICC, International Union Against Cancer; pre-, preoperative; CEA, carcinoembryonic antigen.

Table 4 Survival outcomes according to risk stratification by Model A and Model B

Model	Prognostic score	Median survival (95% CI), months	1-year survival	2-year survival	3-year survival	4-year survival	5-year survival
Model A
Low-risk group	0–6	61.0 (58.2–63.8)	95.3%	84.6%	74.8%	70.8%	64.6%
High-risk group	>6	29.9 (20.3–31.4)	76.5%	52.5%	39.9%	32.2%	20.8%
Model B
Low-risk group	<4	66.4 (63.0–69.8)	99.3%	96.7%	86.9%	84.5%	78.6%
Intermediate-risk group	4–7	51.6 (47.7–55.4)	90.7%	73.9%	62.4%	56.4%	50.5%
High-risk group	>7	29.3 (22.5–36.2)	73.2%	46.4%	33.8%	26.6%	16.2%

Abbreviation: CI, confidence interval.

Figure 2 Kaplan–Meier analysis of overall survival, according to risk prognostic score from Model A (two classes, A) and Model B (three classes, B).

Figure 3 The relationship between 5-year survival and UICC stage classification of patients in Models A and B.

Notes: (A and B) Diagrams of 5-year survival for prognostic score Models A and B within UICC stage classification. (C) Percentage and 5-year survival rate of Models Aand B according to UICCstage.
Abbreviation: UICC, International Union Against Cancer.

Figure 4 Kaplan–Meier curves of overall survival (OS) in gastric cancer patients according to adjuvant chemotherapy with or without paclitaxel (A and B), oxaliplatin (C and D), and cisplatin (E and F) stratified by Model A.

Figure 5 Kaplan–Meier curves depicting OS of gastric cancer patients according to the number of cytotoxic agents stratified by Model A (A and B) and Model B (C–E).

Abbreviation: OS, overall survival.

Figure S1 Flow chart outlining patient selection.

Figure S2 Maximally selected log-rank statistics plot for optimal cutoff point identification in Model A.

Figure S3 ROC analysis of two prognostic models compared with TNM alone to predict patient probability for 5-year survival.

Abbreviation: ROC, Receiver Operating Characteristic curve.

Figure S4 Kaplan–Meier curves of OS in gastric cancer patients according to adjuvant chemotherapy with or without taxol (A–C), oxaliplatin (D–F), and cisplatin (G–I) stratified by Model B.

Abbreviation: OS, overall survival.

Table S1 Adjuvant chemotherapy regimens

Adjuvant regimen	N	%	Adherence N	Adherence rate (%)
Total	579	100.0	331	57.2
Oxaliplatin/paclitaxel/5-FU	214	37.0	125	58.4
Oxaliplatin/capecitabine	95	16.4	69	72.6
Paclitaxel/capecitabine	60	10.4	35	58.3
Oxaliplatin/S-1	43	7.4	27	62.8
Paclitaxel/5-FU	40	6.9	12	30.0
Oxaliplatin/5-FU/leukovorin	37	6.4	19	51.3
Paclitaxel/S-1	30	5.2	16	53.3
5-FU/cisplatin	22	3.8	10	45.5
Capecitabine	21	3.6	13	61.9
Oxaliplatin/paclitaxel	5	0.9	1	20.0
S-1	12	2.1	4	33.3

Note: Paclitaxel in the study is Taxol only

Abbreviation: FU, fluorouracil.

Table S2 Adjuvant chemotherapy regimens and dosing schedules

Regimen	Schedules
FOLFOX6	85 mg/m^2 oxaliplatin, 400 mg/m^2 leucovorin, and 400 mg/m^2, 5-FU iv D1 followed by
	2,400 mg/m^2 civ 46–48 h, q2w 8 cycles
SOX	S-1 40–60 mg bid, D1–14, oxaliplatin 130 mg/m^2, iv drip for 2 h, D1, q3W 8 cycles
XELOX	130 mg/m^2 oxaliplatin D1 and 1,000 mg/m^2 capecitabine bid, po, D1–14, q3W 8 cycles
Oxaliplatin/paclitaxel/5-FU	Paclitaxel 80 mg/m^2 iv D1,8, oxaliplatin 30 mg/m^2, iv drip for 2 h, D1, q3W 8 cycles
POX	Paclitaxel 80 mg/m^2 iv D1,8, oxaliplatin 130 mg/m^2 iv, D1, q3W 8 cycles
Paclitaxel/capecitabine	Paclitaxel 80 mg/m^2 iv D1,8, 1,000 mg/m^2 bid, po, D1–14, q3W 8 cycles
Paclitaxel/5-FU	Paclitaxel 80 mg/m^2 iv D1,8, 5-Fu 300 mg/m^2 civ D1–5, q2W 8–10 cycles
Paclitaxel/S-1	Paclitaxel 80 mg/m^2 iv D1,8, q3W 8 cycles
CF	5-FU iv D1 followed by 2,400 mg/m^2 civ 46–48 h, cisplatin 70–100 mg/m^2 iv D1, q3W 8 cycles
Capecitabine	1,000 mg/m^2 bid, po, D1–14, q3W 8 cycles
S-1	80 mg/m^2, po, D1–28, continuous 4 weeks stop 2 weeks

Abbreviations: FU, fluorouracil; iv, intravenous; po, orally; h, hours; civ, continuous intravenous infusion.