Impact of time from diagnosis to chemotherapy in advanced gastric cancer: A Propensity Score Matching Study to Balance Prognostic Factors

Table 1 Characteristics of patients with advanced gastric cancer

Characteristics	Total	Early WT	Elective WT	P value
No.	110	46	64
Disease status Unresectable/ recurrent	103/7	43/3	60/4	1.000
Waiting time (WT), d, median (IQR)	17 (12.5, 26)	10 (7, 13)	24 (19. 36)	P < 0.0001
Male sex, n, %	79, 72%	34, 74%	45, 70%	0.6743
Age, yr, median (IQR)	70 (64, 78)	71 (64, 80)	67 (62, 75)	0.1490
BMI, median (IQR)	20.3 (18.6, 22.8)	21.1 (19.0, 22.8)	19.9 (18.4, 22.9)	0.5298
Diabetes mellitus, n, %	15, 14%	5, 11%	10, 17%	0.4158
Hypertension, n, %	36, 35%	16, 36%	20, 34%	1.000
Dementia, n, %	2, 2%	1, 2.2%	1, 1.7%	1.000
Chronic kidney disease, n, %	43, 41%	19, 42%	24, 40%	0.8434
Charlson comorbidity index, median (IQR)	0 (0, 1)	0 (0, 0.5)	0 (0, 1)	0.3884
Low/medium/high/missing	73 (70%)/29 (28%)/3 (3%), 5(5%)	34/9/2/1	39/20/1/4
PS 0-1, n, %	95, 86%	41, 89%	54, 84%	0.8234
Histology type, intestinal n, %	40, 36%	18, 39%	22, 35%	0.5228
HER 2 IHC 3+< or FISH (+), n, %	26, 26%	12, 26%	14, 22%	0.6080
Gastric cardia tumor site, n, %	25, 23%	7, 15%	18, 29%	0.1130
Target lesion, n, %	91, 91%	41, 91%	50, 91%	1.000
No. of metastatic lesions ≤ 1, %	39, 35%	16, 35%	23, 36%	1.000
CEA, median (IQR)	6.5 (2.2, 40.9)	6.5 (2.4, 80)	5.7 (2, 25)	0.4624
CA19-9, median (IQR)	22 (5, 810)	54.5 (4.5, 2289)	17 (5, 630)	0.7326
Hb, g/dL, median (IQR)	11.3 (9.2, 12.7)	11.3 (9.3, 12.9)	11.2 (9.1, 12.7)	0.8995
Alb, g/dL, median (IQR)	3.3 (3, 3.7)	3.2 (2.8, 3.5)	3.4 (3, 3.7)	0.0129
CRP, mg/dL, median (IQR)	0.63 (0.15, 2.2)	1.3 (0.47, 4.6)	0.47 (0.08, 1.71)	0.0015
NLR, median (IQR)	3.8 (2.7, 6.5)	4.5 (3.1, 9.3)	3.4 (2.3, 5.4)	0.0112
Clinical symptoms, yes, %	93, 84.6%	41, 89.1%	52, 81.2%	0.2970

Chronic renal disease is defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min. The Charlson comorbidity index encompasses 19 medical conditions weighted 1–6 with total scores ranging from 0-37. For each condition, the scores reflected the risk as follows: 0, low; 1-2, medium; 3-4, high; and ≧5, very high risk. IQR: Interquartile range; PS: Performance status; BSC: Best supportive care; CTx: Chemotherapy; Alb: Albumin; CRP: C-reactive protein; NLR: Neutrophil/lymphocyte ratio.

Table 2 Chemotherapy regimens and responses of patients with advanced gastric cancer

Characteristics	Total	Early WT	Elective WT	P value
No.	110	46	64
Chemotherapy; combination	76, 70%	27, 59%	49, 78%	0.0371
Agents
5-FU	104	40, 85%	64, 93%	0.3532
Platinum	79	26, 55%	53, 77%	0.0100
Irinotecan	1	1, 2.1%	0, 0%	1.0000
Taxane	14	8, 17%	6, 8.7%	0.2460
Trastuzumab	19	9, 19%	10, 14%	0.6110
Ramucirumab	1	0, 0%	1, 1.5%	0.4072
Response to first-line chemotherapy
CR	1, 0.91%	0, 0%	1, 1.6%	0.1721
PR	23, 20.9%	7, 15.2%	16, 25%
SD	47, 42.7%	17, 37.0%	30, 46.9%
PD	16, 14.6%	10, 21.7%	6, 9.4%
NE	23, 20.9%	12, 26.1%	11, 17.2%
RR	24, 21.8%	7, 15.2%	17, 26.6%
DCR	71,64.5%	24, 52.8%	47, 73.5%
Second-line chemotherapy, yes1	54, 63.5%	24, 58.5%	30, 68.2%	0.3770

¹Twenty-five patients were not evaluated (during first-line chemotherapy). WT: Waiting time; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; NE: Not evaluated; RR: Response rate; DCR: Disease control rate.

Table 3 Univariate and multiple logistic regression analyses of prognosis in advanced gastric cancer patients

	Univariate analysis			Multivariate analysis
Category	HR	96%CI	P value	HR	96%CI	P value
Early WT	1.502	0.982-2.28	0.0605	1.132	0.721-1.760	0.5857
CRP	1.12	1.050-1.185	0.0010	1.091	1.001-1.173	0.0335
NLR	1.03	0.99-1.057	0.0563	0.990	0.954-1.021	0.5520
Alb	0.514	0.354-0.750	0.0005	0.539	0.357-0.818	0.0038
Chemotherapy (combination)	0.669	0.431-1.065	0.0893	0.504	0.408-0.841	0.0094

HR: Hazard ratio; WT: Waiting time; Alb: Albumin; CRP: C-reactive protein; NLR: Neutrophil/lymphocyte ratio.

Table 4 Using 1:1 propensity score matching including C-reactive protein level, Alb level, and the administration of combination chemotherapy, we obtained a total of 48 matched patients in the early and elective waiting time groups (this table shows the characteristics of the propensity-matched patients with advanced gastric cancer)

	Propensity-matched cohort
Characteristics	Early WT	Elective WT	P value
No.	24	24
Disease status Unresectable/recurrent	23/1	20/4	0.3475
Waiting time (WT), d, median (IQR)	12 (8, 13)	22.5 (19.3, 33.8)	< 0.0001
Male sex, n, %	18, 75%	18, 75%	1.0000
Age, years, median (IQR)	68 (61, 72)	73.5 (63, 79)	0.1635
BMI, median (IQR)	20.7 (18.8, 22.5)	20.9 (19.3, 23.2)	0.5727
Diabetes mellitus, n, %	3, 13%	3, 13%	1.0000
Hypertension, n, %	10, 42%	9, 39%	1.0000
Dementia, n, %	1, 4%	1, 4%	1.000
Chronic kidney disease, n, %	9, 38%	10 42%	0.7702
Charlson comorbidity index score, median (IQR)	0 (0, 0)	0 (0, 0)	0.9611
Low/medium/high/missing	20, 2, 2, 0	19, 3, 1, 1	0.7348
PS 0-1, n, %	23, 96%	20, 87%	0.5347
Histology type, intestinal, n, %	8, 33%	12, 50%	0.3442
HER 2 IHC 3+< or FISH (+), n, %	7, 29%	8, 33%	1.0000
Gastric cardia tumor site, n, %	2, 8%	7, 29%	0.1365
Target lesion, n, %	23, 96%	19, 86%	0.3364
No. of metastatic lesions ≤ 1	9, 38%	10, 42%	0.8541
CEA, median (IQR)	6.7 (2.2, 91)	8.8 (4.9, 75.5)	0.7175
CA19-9, median (IQR)	86 (3, 851)	27 (7, 6583)	0.6282
Hb, g/dL, median (IQR)	11.3 (9.7, 12.9)	11 (7.7, 12.3)	0.5226
Alb, g/dL, median (IQR)	3.3 (2.9, 3.6)	3.2 (3, 3.7)	0.8848
CRP, mg/dL, median (IQR)	0.59 (0.26, 1.97)	0.48 (0.13, 1.94)	0.5707
NLR, median (IQR)	3.9 (3.0, 6.7)	3.1 (2.4, 5.0)	0.1576
Monotherapy; combination	7; 17	7; 17	1.0000

Chronic renal disease is defined as an eGFR (estimated glomerular filtration rate) < 60 mL/min. The Charlson comorbidity index encompasses 19 medical conditions weighted 1-6 with total scores ranging from 0-37. For each condition, the scores reflected the risk as follows: 0, low; 1-2, medium; 3-4, high; and ≥ 5, very high risk. IQR: Interquartile range; Alb: Albumin; CRP: C-reactive protein; NLR: Neutrophil/lymphocyte ratio.