Predictive factors for early distant metastasis after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Table 6 Summaries of studies on neoadjuvant chemotherapy without radiotherapy

Study	Design	n	Eligibility	NAC regimen	CRT regimen	AC regimen	Response	Compliance	Recurrence	Survival
Koizumi et al[17]	Phase II single-arm	30	Lower edge under S2, cT3-4	FOLFOX (× 6)	-	-	pCR 6.7%	NAC 93.3%	LR 2 pts; DM 5 pts	3Y-OS 95.7%
FORTUNE[18]	Phase II single-arm	106	cT3-4, cN1-2, distal edge < 12 cm from AV	mFOLFOXIRI (× 4-6)	RT 50.4Gy/28Fx’s; mFOLFOX61 or RT 25Gy/5Fx’s	mFOLFOX6(× 6)	pCR 20.4%; pCR 17.4% after NAC	NAC 100%	-	-
Ishii et al[19]	Prospectivesingle-arm	26	cT3-4 with cN0-2	IFL (× 2)	-	-	Downstaging 57.0%; pCR 3.8%	NAC 100%	-	5Y-OS 84.0%
FOWARC[20,21]	Phase III RCT	165	cT3-4, N1-2	-	RT 45Gy/25Fx’s 5-FU	5-FU (× 7)	pCR 14.0%	CRT 88.4%	LR 8.0%	3Y-OS 91.3%
		165		-	RT 45Gy/25Fx’s mFOLFOX6	mFOLFOX (× 7)	pCR 27.5%	CRT 94.9%	LR 7.0%	3Y-OS 89.1%
		165		mFOLFOX6 (× 4-6)	-	mFOLFOX6(× 6-8)	pCR 6.5%	NAC 94.5%	LR 8.3%	3Y-OS 90.7%
Schrag et al[22]	Phase II single-arm	32	Distal edge within 5-12cm from AV, cT3N-, cT3N+	mFOLFOX6/bevacizumab (× 6)	RT 50.4Gy/28Fx’s 5-FU1	FOLFOX	pCR 25.0%	NAC 93.8%	LR 0; DM 12.5%	4Y-OS 91.0%
N-SOG 03[23]	Phase II single-arm	32	MR defined disease: Inferior margin below the S2 lower margin, MRF involved or threatened, cT3b-d, cT4, cN2	CAPOX/bevacizumab (× 4)	-	-	T down staging 54.0% after surgery pCR 25.0%	NAC 79.2%; CRT 94.7%	-	-
GEMCAD 0801[24,32]	Phase II single-arm	46	MR defined disease: Distal edge > 5 cm from AV, cT3 (≥ 2 mm from MRF)	CAPOX/bevacizumab (× 4)	-	-	pCR 19.5%	NAC 95.6%	LR 2 pts; DM 8 pts; Both 1 pt	-

¹Chemoradiotherapy if any progression after neoadjuvant chemotherapy.

NAC: Neoadjuvant chemotherapy; CRT: Chemoradiotherapy; RT: Radiotherapy; AC: Adjuvant chemotherapy; OS: Overall survival; LR: Local recurrence; DM: Distant metastasis; MR: Magnetic resonse; AV: Anal verge; MRF: Mesorectal fascia; CAPOX: Capecitabine/oxaliplatin; IFL: Irinotecal/fluorouracil/leukovorin; pCR: Pathological complete response; RCT: Randomized controlled trial.