Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines

Table 3 Short-term and long-term effects of different pre/perioperative chemotherapy regimens

Ref.	Region	Regimen	n	Median age	EGJ/gastric (%)	pT stage (%)					pN stage (%)				Short-term effect		Long-term effect(mo; yr)
						0	1	2	3	4	0	1	2	3	aSurgery/R0 (%)	Response
Mongan et al[60], 2015	EU	EOX	59	65	71/29	6	9	23	58	4	30	44	17	9	80/54	Mandard et al[115], TRG 1-3: 34%	Median OS: 22 mo; 4-yr survival: 47%; recurrence rate: 40%; median time to recurrence: 13 mo
Bichev et al[59], 2015	EU	ECF/mECF	77	62.1	61/40	0b		4	91	5	14	86			88/69	Becker et al[116], TRG 1 + 2: 44.2%	5-yr cumulative survival: 36.3%; median OS: 23.7 mo; 5-yr TSS: 42.2%; median TSS: 32.9 mo; recurrence rate: 32%
Mingol et al[58], 2015	EU	ECF/ECX	53	64	17/83	33			67		35	17	48		91/72	Becker et al[116], TRG 1a + 1b: 17%	5-yr OS: 18%; 5-yr DSS: 22%; recurrence rate: 61.9%
Achilli et al[46], 2017	EU	ECF/ECX	67	67	0/100	0	8	18	65	9	NA	NA	73		99/96	CR + PR: 37%; Becker TRG 1: 29%	Median OS: 36.6 mo; median DFS: 25.7 mo; recurrence rate: 54%
REECE-SMITH et al[45], 2012	EU	ECF/ECX	100	66	68/32	4	9	32	46	9	50	32	14	5	78/76	Histological regression > 50%: 45.8%	Median survival: 31.7 mo; 2-yr survival: 53%
Favi et al[48], 2017	EU	FLOT	40	61.5	100/0	12	15	17	43	10	40	17	28	15	97/85	Cologne Regression Scale 1-3: 52%	1-yr OS: 72%; 2-yr OS: 60%; 3-yr OS: 37%; median OS: 2.4 yr
Al-Batran et al[47], 2017	EU	FLOT	51	66	39/61	0b		18	69	8	26	75			96/78	NA	Median OS and PFS not achieved
Schulz et al[50], 2015	EU	FLOT	58	61	59/38	20	12	16	40	8	54	16	16	10	86/74	Becker et al[116], TRG 1a + 1b: 40%	1-yr survival: 79.3%; 1-yr PFS: 67.2%; median DFS: 32.9 mo
Lorenzen et al[49], 2013	EU	FLOT	21	69	62/38	10	48		5		29	38			71/67	CR + PR: 59.1%	1.5-yr OS: 78%; 2-yr OS: 78%; median PFS: 21.1 mo
		FLO	22	71.5	41/59	0	68		5		32	41			77/68	CR + PR: 18.2%	1.5-yr OS: 70%; 2-yr OS: 56%; median PFS: 12.0 mo
Yoshikawa et al[52], 2016	AS	SC-2	21	66	33/67	0			5	95	5	60	20	15	95/81	NA	3-yr OS: 67%
		SC-4	20	63	25/75	0			5	95	20	40	20	20	90/75	NA	3-yr OS: 55%
Tsuburaya et al[55], 2014	AS	SC	53	63	NA	4	14	47	33	2	16	10	43	31	94/82	CR + PR: 65%; JCGC[108] grade 1b-3: 51%	3-yr OS: 59%; 5-yr OS: 53%; 3-yr and 5-yr RFS: 50%
Kochi et al[54], 2017	AS	SC	50	64	0/100	NA	12	8	40	36	22	14	32	30	98/88	pCR: 2%; clinical response for LN: 75.5%, for primary tumor: 59.2%	3-yr OS: 48%; 3-yr RFS: 42%
Ott et al[53], 2003	EU	FLP	49	58	0/100	0	10	55	24	12	26	36	21	17	86/76	Major pathological tumor regression: 17%	Median survival: 25.4 mo (for ITT patients) and 32 mo (for R0 patients); recurrence rate: 62.5%; median recurrence: 19 mo
Li et al[51], 2012	AS	FOLFOX	33	65	0/100	12	6	12	61	9	36	33	27	3	100/91	CR + PR: 69.7%; JRSGC[117] grade 2-3: 39.4%	Mean survival: 74 mo; 4-yr OS: 78%; 4-yr DFS: 78%
Xue et al[61], 2018	AS	SOX	25	≥ 65: 48%	0/100	12	8	36	8	36	60	16	8	16	100/100	JCGC[108] grade 2-3: 40%	5-yr OS: 70%
		CAPOX	25	≥ 65: 24%	0/100	4	8	32	20	36	44	20	16	20	100/100	JCGC[108] grade 2-3: 36%
Yu et al[57], 2019	AS	XELOX	54	65	30/70	13	13	17	33	25	31	15	31	23	91/83	CR + PR: 50%; JCGC[108] grade 1b-3: 41.6%	Median OS: 30.77 mo; 3-yr OS: 47.2%; disease progression: 55.6%; median PFS: 20.1 mo; 3-yr PFS: 43.8%
Feng et al[56], 2015	AS	SOX	80	60	40/60	15	11	30	19	25	59	16	14	11	100/95	CR + PR: 68.8%; pCR: 12.5%	NA

^a: Some data were amended in order to increase comparability.

^b: T and N stages in this study were clinical stages. EU: Europe; AS: Asia; EOX: Epirubicin, oxaliplatin and capecitabine; ECF: epirubicin, cisplatin and fluorouracil; mECF: ECF modifications; ECX: Epirubicin, cisplatin and capecitabine; FLOT: Docetaxel, fluorouracil, leucovorin and oxaliplatin; FLO: Fluorouracil, leucovorin and oxaliplatin; SC: S-1 and cisplatin; SC-2/4: S-1 and cisplatin for 2 cycles/4 cycles; FLP: 5-FU, cisplatin and leucovorin; FOLFOX: Oxaliplatin, fluorouracil and leucovorin; SOX: S-1 and oxaliplatin; CAPOX: Capecitabine and oxaliplatin; XELOX: Capecitabine and oxaliplatin; EGJ: Esophagogastric junction; LN: Lymph node; TRG: Tumor regression grade; JRSGC: Japanese research society for gastric cancer; JCGC: Japanese classification of gastric cancer; CR: Complete regression; PR: Partial regression; pCR: Pathological complete regression; OS: Overall survival; TSS: Tumor specific survival; DSS: Disease specific survival; DFS: Disease free survival; PFS: Progression-free survival; RFS: Relapse-free survival; ITT: Intention to treat; NA: Not available.