Early vs conventional initiation of adjuvant chemotherapy in advanced gastric cancer: A propensity-matched outcomes study

Table 1 Characteristics of patients before and after propensity score matching, n (%)

Characteristics	Before PSM (n = 219)				After PSM (n = 63)
	Conventional (n = 198)	Early (n = 21)	P value	SMD	Conventional (n = 42)	Early (n = 21)	P value	SMD
Sex			0.854	0.044			0.366	0.246
Male	128 (64.6)	14 (66.7)			23 (54.8)	14 (66.7)
Female	70 (35.4)	7 (33.3)			19 (45.2)	7 (33.3)
Age, years
< 65	136 (68.7)	11 (52.4)			27 (64.3)	12 (57.1)
≥ 65	62 (31.3)	10 (47.6)			15 (35.7)	9 (42.9)
Median, IQR	60.00 (54.00, 65.25)	63.00 (58.50, 70.00)	0.118	0.221	62.50 (57.00, 68.25)	63.00 (58.50, 70.00)	0.890	0.043
BMI, kg/m2
< 23	154 (77.8)	14 (66.7)			30 (71.4)	14 (66.7)
≥ 23	44 (22.2)	7 (33.3)			12 (28.6)	7 (33.3)
Median, IQR	20.83 (18.83, 22.54)	22.27 (20.74, 24.14)	0.015	0.573	21.34 (18.00, 24.16)	22.27 (20.74, 24.14)	0.135	0.448
ECOG grade			0.174	0.305			0.858	0.048
0	65 (32.8)	10 (47.6)			19 (45.2)	10 (47.6)
1-2	133 (67.2)	11 (52.4)			23 (54.8)	11 (52.4)
Stage			0.367	0.220			0.668	0.117
Stage II	56 (28.3)	4 (19.0)			10 (23.8)	4 (19.0)
Stage III	142 (71.7)	17 (81.0)			32 (76.2)	17 (81.0)
PNI			0.819	0.049			1.000	< 0.001
Yes	182 (91.9)	19 (90.5)			38 (90.5)	19 (90.5)
No	16 (8.1)	2 (9.5)			4 (9.5)	2 (9.5)
LVI			0.597	0.128			0.445	0.214
Yes	171 (86.4)	19 (90.5)			35 (83.3)	19 (90.5)
No	27 (13.6)	2 (9.5)			7 (16.7)	2 (9.5)
Histology			0.381	0.105			0.271	0.393
Differentiated	84 (42.4)	11 (47.6)			28 (66.7)	11 (47.6)
Undifferentiated	114 (57.6)	10 (52.4)			14 (33.3)	10 (52.4)
Chemotherapy regimen			0.002				0.136
mFOLFOX-6	14 (7.1)	6 (28.6)		0.858	5 (11.9)	6 (28.6)		0.424
SOX	102 (51.5)	5 (23.8)		0.596	19 (45.2)	5 (23.8)		0.462
XELOX	82 (41.4)	10 (47.6)		0.123	18 (42.9)	10 (47.6)		0.094

PSM: Propensity score matching; SMD: Standardized mean difference; IQR: Interquartile range; BMI: Body mass index; ECOG: Eastern Cooperative Oncology Group; PNI: Perineural invasion; LVI: Lymphovascular invasion; mFOLFOX-6: 5-fluorouracil plus calcium folinate plus oxaliplatin; SOX: Tegafur plus oxaliplatin; XELOX: Capecitabine plus oxaliplatin.

Table 2 Grade 3/4 adverse events and adherence/feasibility of each treatment group (n = 63), n (%)

	Conventional (n = 42)	Early (n = 21)	P value
RDI (%), mean ± SD	68.58 ± 27.64	65.34 ± 28.07	0.587
Median (IQR)	73.4 (51.88, 96.25)	67.50 (46.38, 95)
Completion rate
4 cycles	34 (81.0)	17 (81.0)	1.000
8 cycles	16 (38.1)	7 (33.3)	0.786
Dose down rate			0.026
None	31 (73.8)	9 (42.9)
Reduction	11 (26.2)	12 (57.1)
Schedule change rates			0.08
None	26 (61.9)	18 (85.7)
Change	16 (38.1)	3 (14.3)
Adverse event
Overall toxicity	18 (42.9)	12 (57.1)	0.285
Related death	0	0	NA
Leukopenia	4 (9.5)	1 (4.8)	0.657
Neutropenia	15 (35.7)	10 (47.6)	0.363
Thrombocytopenia	8 (19.0)	3 (14.0)	0.639
Anorexia	12 (28.6)	9 (42.9)	0.257
Vomiting	10 (24.4)	4 (19.0)	0.085
Neurotoxicity	1 (2.4)	2 (9.5)	0.219
Diarrhea	3 (7.1)	2 (9.5)	0.742

RDI: Relative dose intensity; IQR: Interquartile range; NA: Not available.

Table 3 Site of first recurrence in each treatment group, n (%)

Site	Conventional (n = 42)	Early (n = 21)	HR for recurrence in the early group (95%CI)	P value	P value1
Total number of relapses	16 (38.1)	9 (42.9)
Local	3 (7.1)	3 (14.3)	2.336 (0.470-11.603)	0.299	0.391
Lymph nodes	3 (7.1)	2 (9.5)	1.459 (0.244-8.733)	0.679	1.000
Hematogenous	4 (9.5)	2 (9.5)	1.636 (0.336-7.312)	0.520	0.677
Peritoneum	11 (26.2)	1 (4.8)	0.418 (0.093-1.887)	0.257	0.048

¹Fisher’s exact test.

Some patients experienced recurrence at more than one site. HR: Hazard ratio; CI: Confidence interval.

Table 4 Multivariate Cox regression for recurrence-free survival

Variable	HR for recurrence	95%CI	P value
Early vs conventional	1.199	0.461-3.121	0.710
Tumor differentiation
Differentiated (reference1)	1
Undifferentiated	2.071	0.929-4.618	0.075
BMI, kg/m2
< 23 (reference1)	1
≥ 23	0.523	0.176-1.554	0.244
Chemotherapy regimen
SOX (reference)	1
XELOX	0.767	0.325-1.809	0.545
mFOLFOX6	0.919	0.144-5.878	0.929

¹The reference category in the Cox model.

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; SOX: Tegafur plus oxaliplatin; XELOX: Capecitabine plus oxaliplatin; mFOLFOX-6: 5-fluorouracil plus calcium folinate plus oxaliplatin.