Impact of preoperative chemoradiotherapy using concurrent S-1 and CPT-11 on long-term clinical outcomes in locally advanced rectal cancer

Table 1 Patient characteristics

Characteristic	n = 82
Age (yr)
Median (range)	64 (34–79)
Sex
Male	60 (73.2)
Female	22 (26.8)
Distance from anal verge (cm)
Median (range)	5.0 (0–8)
Size of tumor (cm)
Median (range)	4.5 (2–9)
Clinical T stage (before chemoradiotherapy)
3	72 (87.8)
4	10 (12.2)
Mesorectal fascia invasion
−	53 (64.6)
+	29 (35.4)
Extramural vascular invasion
−	46 (56.1)
+	36 (43.9)
Clinical N stage (before chemoradiotherapy)
−	36 (43.9)
+	46 (56.1)
Subgroup of locally advanced rectal cancer
Bad	50 (61.0)
Ugly	32 (39.0)
UGT1A1 polymorphism (in 48 patients)
Wild type	25 (52.1)
Mutant type	23 (47.9)

Data are n (%) unless otherwise shown.

Table 2 Acute toxicity according to Common Terminology Criteria for Adverse Events 4.0, on patients receiving chemoradiotherapy, n (%)

Toxicity	n = 82
	Any Grade	Grade 3 or 4
Hematological toxicity
Neutropenia	56 (68.3)	16 (19.5)
Leukopenia	59 (72.0)	15 (18.3)
Febrile neutropenia	3 (3.6)	3 (3.6)
Thrombocytopenia	11 (13.4)	0
Nonhematological toxicity
Diarrhea	53 (64.6)	22 (26.8)
Anorexia	20 (24.4)	1 (1.2)
Fatigue	15 (18.3)	0
Nausea	13 (15.9)	0

Table 3 Associations between toxicity, feasibility and treatment effect and UGT1A1 polymorphisms, n (%)

	Wild type (n = 25)	Mutant type (n = 23)	P value
Toxicity
Hematological toxicity (Grade 3 or 4)	0	11 (47.8)	< 0.01
Nonhematological toxicity (Grade 3 or 4)	8 (32.0)	6 (26.1)	0.65
Feasibility (%)
S-1 dose intensity (mean ± SD)	90.9 ± 0.2	89.0 ± 0.2	0.38
CPT-11 dose intensity (mean ± SD)	93.0 ± 0.3	88.2 ± 0.2	0.26
Treatment effect
Good response	18 (72.0)	22 (95.7)	< 0.01
Poor response	7 (28.0)	1 (4.3)
Pathological complete response	5 (20.0)	6 (26.1)	0.61

CPT-11: Irinotecan; S-1: Tegafur/gimeracil/oteraci.

Table 4 Postoperative surgical complications, n (%)

Complication	n = 82
	Any grade	Grade 3
Pelvic infection	15 (18.3)	9 (11.0)
Anastomosis leakage1	9 (12.2)	7 (9.5)
Ileus	11 (13.4)	5 (6.1)
Bleeding	1 (1.2)	1 (1.2)
Surgical site infection	2 (2.4)	0
Urinary dysfunction	8 (9.8)	0
Venous thromboembolic event	1 (1.2)	0
Re-operation	0	0

¹The patients who performed abdominoperineal resection was excluded, and anastomosis leakage rates were calculated. SSI: Surgical site infection; VTE: Venous thromboembolic event.

Table 5 Pathological tumor characteristics, n (%)

Pathological tumor characteristics	n = 82
ypT stage
0	13 (15.9)
1	5 (6.1)
2	21 (25.6)
3	25 (42.7)
4	8 (9.8)
ypN stage
−	65 (79.3)
+	17 (20.7)
yp TNM stage1
0	13 (15.9)
I	20 (24.4)
II	32 (39.0)
III	17 (20.7)
Residual tumor classification
R0	79 (96.3)
R1	3 (3.7)
R2	0
Histology
well/moderately differentiated	66 (80.5)
Poorly differentiated/mucinous/signet	16 (19.5)
T downstaging
−	41 (50.0)
+	41 (50.0)
N downstaging
−	46 (56.1)
+	36 (43.9)
Tumor regression grade
1a	18 (22.0)
1b	12 (14.6)
2	39 (47.6)
3	13 (15.9)
Adjuvant chemotherapy
–	56 (68.3)
+	26 (31.7)

¹According to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. R0: No residual tumor confirmed microscopically; R1: Microscopic tumor residue; R2: Macroscopic tumor residue.

Table 6 Multivariate prognostic analysis for local recurrence-free survival and relapse-free survival

Factors	n	LFS						RFS
		Univariate			Multivariate			Univariate			Multivariate
		OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
Sex
Female	22
Male	60	1.91	0.21-17.7	0.56				1.13	0.36-3.60	0.83
Location from anal verge (cm)
≥ 5.0	29
< 5.0	53	1.10	0.19-6.41	0.91				1.89	0.61-5.89	0.26
Tumor diameter (cm)
< 4.5	42
≥ 4.5	40	2.00	0.86-2.89	0.43				0.63	0.22-1.74	0.37
cT
3	72
4	10	4.25	0.67-27.0	0.10	1.97	0.23-17.1	0.54	3.80	0.97-14.9	0.06	2.05	0.39-10.7	0.39
cN
−	36
+	46	1.62	0.28-9.38	0.59				1.25	0.34-2.60	0.90
Mesorectal fascia invasion
−	53
+	29	4.08	0.70-23.8	0.10	2.88	0.39-21.5	0.30	7.31	2.39-22.4	< 0.01	5.82	1.68-20.2	< 0.01
Extramural vascular invasion
−	46
+	36	2.75	0.47-15.9	0.24				3.15	1.10-9.03	0.03	3.42	1.02-11.5	0.04
Lateral lymph node (> 7.0 mm)
−	74
+	8	5.83	0.88-38.7	0.09	4.71	0.65-34.2	0.12	2.01	0.44-9.29	0.36
Histology
Well/moderately differentiated	66
Poorly differentiated/mucinous/signet	16	0.81	0.09-7.49	0.86				1.55	0.46-7.58	5.15

CI: Confidence interval; LFS: Local recurrence-free survival; OR: Odds ratio, RFS: Relapse-free survival.