Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

Table 1 Patient characteristics

Characteristic		Standard therapy, n = 72, (%)	TNT, n = 89, (%)	P value
Age in year	< 65	29 (40)	66 (74)	< 0.001
	≥ 65	43 (60)	23 (26)
	Range	40-84	33-79
	mean [SD]	65.4 [10.5]	57.5 [10.1]	< 0.001
Sex	M	45 (63)	54 (61)	0.813
	F	27 (38)	35 (39)
PS WHO	0	48 (67)	67 (75)	0.229
	1	24 (33)	22 (25)
High-risk factors for failure	cT4	15 (21)	33 (37)	0.025
	cN2	49 (68)	62 (70)	0.827
	MRF+	39 (54)	66 (74)	0.008
	EMVI+	27 (38)	65 (73)	< 0.001
	Lateral node	15 (21)	8 (9)	0.033
cTN	T2N2	1 (1)	1 (1)	0.1381
	T3N0	1 (1)	0 (0)
	T3N1	21 (29)	20 (22)
	T3N2	34 (47)	35 (39)
	T4N1	1 (1)	7 (8)
	T4N2	14 (19)	26 (29)
Distance from anal verge in cm	≤ 5	27 (38)	29 (33)	0.370
	5.1-10	37 (51)	43 (48)
	≥ 10.1	8 (11)	17 (19)

¹Likelihood-ratio test.

EMVI: Extramural vascular invasion; MRF: Mesorectal fascia; PS: Performance status; TNT: Total neoadjuvant treatment; WHO: World Health Organization.

Table 2 Treatment characteristics

Characteristic		Standard therapy, n = 70, (%)	TNT, n = 82, (%)	P value
pCR		5 (7)	19 (23)	0.007
CR		7 (10)	23 (26)	0.009
NAR score	mean [SD]	16.8 [12.9]	10.7 [10.8]	0.002
NAR classes	< 8	9 (13)	35 (43)	< 0.001
	8-16	38 (56)	33 (40)
	> 16	21 (31)	14 (17)
Surgery	R0	65 (93)	78 (95)	0.4451
	R1	4 (6)	4 (5)
	R2	1 (1)	0 (0)
Weeks to stoma closure	mean [SD]	32.8 [18.6]	20.1 [10.9]	< 0.001

¹Likelihood-ratio test.

CR: Complete response; NAR: Neoadjuvant rectal; pCR: Pathological complete response; TNT: Total neoadjuvant treatment.

Table 3 Treatment compliance during chemoradiotherapy and systemic chemotherapy, n (%)

	Standard therapy during CRT	TNT	P value
Patients who received CRT	72 (100)	88 (99)	0.2751
Patients who received RT	0 (0)	1 (1)
Full-dose ChT (CAP or 5-FU + LV)	62 (86)	67 (75)	0.087
Modification of concomitant ChT	10 (14)	22 (25)
Modification of RT	1 (1)	0 (0)
	During adjuvant ChT	During systemic ChT
Without ChT due to pCR	5 (7)	0 (0)
Patients who received ChT	50 (72)	89 (100)
All planned cycle
6c of systemic ChT (CAP or CAPOX)	34 (68)	76 (85)	0.0481
Other alternative schemes	4 (8)	2 (2)
No	12 (24)	11 (12)
Full-dose
6c of systemic ChT (CAP or CAPOX)	25 (50)	56 (63)	0.1581
Other alternative schemes	4 (8)	2 (2)
No	21 (42)	31 (35)

¹Likelihood-ratio test.

5-FU: 5-fluorouracil; c: Cycle; CAP: Capecitabine; CAPOX: Capecitabine and oxaliplatin; ChT: Chemotherapy; CRT: Chemoradiotherapy; LV: Leucovorin; pCR: Pathological complete response; RT: Radiotherapy; TNT: Total neoadjuvant treatment.

Table 4 Acute toxicity in all periods in both treatment groups

Toxicity	Standard therapy, n (%)	TNT, n (%)	P value
During systemic ChT			0.0371
Without	12 (24)	16 (18)
Grade 1-2	31 (62)	70 (79)
Grade 3	7 (14)	3 (3)
During CRT			0.5531
Without	13 (18)	21 (24)
Grade 1-2	57 (79)	64 (72)
Grade 3-4	2 (3)	4 (4)
Postoperative complications			0.140
Without	43 (61)	62 (76)
Grade 1-2	18 (26)	15 (18)
Grade 3-5	9 (13)	5 (6)

¹Likelihood-ratio test.

ChT: Chemotherapy; CRT: Chemoradiotherapy; TNT: Total neoadjuvant treatment.

Table 5 Acute toxicity during systemic chemotherapy in both treatment groups

Toxicity during systemic ChT	Adjuvant ChT (standard therapy), 50 patients						During induction and consolidation ChT (TNT), 89 patients
	Grade 1-2		Grade 3		Grade 4		Grade 1-2		Grade 3		Grade 4
Thrombocytopenia	7	14%	0		0		11	12%	0		0
Anaemia	15	30%	0		0		12	13%	0		0
Neutropenia	3	6%	0		0		8	9%	0		0
Diarrhoea	6	12%	1	2%	0		10	11%	0		0
Nausea	2	4%	1	2%	0		29	33%	0		0
Vomiting	2	4%	1	2%	0		8	9%	0		0
Hand foot syndrome	15	30%	5	10%	0		10	11%	1	1%	0
Paraesthesia	1	2%	0		0		54	61%	0		0
Acute renal failure	1	2%	0		0		0		0		0
Rectal fistula	0		1	2%	0		0		0		0
Stoma site infection	1	2%	1	2%	0		0		0		0
Hepatotoxicity	0		0		0		3	3	0		0
Infection	5	10%	0		0		2	2%	1	1%	0
Chest pain	0		0		0		1	1%	0		0
Thromboembolism	5	10%	0		0		1	1%	1	1%	0
Ileus	1	2%	0		0		1	1%	0		0
Enterocolitis	0		0		0		1	1%	0		0
Without toxicity	12 (24%)						16 (18%)

ChT: Chemotherapy; TNT: Total neoadjuvant treatment.