Radiotherapy-free neoadjuvant strategy using sintilimab plus XELOX in locally advanced rectal cancer: A single-arm phase II trial

Table 1 Baseline characteristics, mean ± SD/n (%)

Characteristic	All patients (n = 41)
Age (years)	61.29 ± 9.48
Gender
Male	30 (73.2)
Female	11 (26.8)
Before treatment BMI (kg/m2)	22.99 ± 3.05
Hypertension	14 (34.1)
Diabetes	5 (12.2)
Smoking	15 (36.6)
Drinking	9 (22.0)
Before treatment clinical T stage
cT2	2 (4.9)
cT3	26 (63.4)
cT4a	13 (31.7)
cT4b	0 (0)
Before treatment clinical N stage
cN0	2 (4.9)
cN1	14 (34.1)
cN2	25 (61.0)
Lateral lymph node ≥ 7 mm	0 (0)
Clinical disease stage before treatment
Stage II (cT3-4N0)	2 (4.9)
Stage III (cT1-4N1-2)	39 (95.1)
CRM
Threatened	8 (19.5)
Negative	33 (80.5)
EMVI
Positive	10 (24.4)
Negative	31 (75.6)
Maximum length of tumor involvement (cm)	4.82 ± 1.55
Less than 4	18 (43.9)
Not less than 4	23 (56.1)
Distance from anal verge (cm)	6.71 ± 3.13
Less than 5	17 (41.5)
Not less than 5	24 (58.5)
Anal canal involvement	0 (0)
Sphincter involvement	0 (0)
Initial CEA level (ng/mL)	7.59 ± 14.68
Less than 5	26 (63.4)
Not less than 5	15 (36.6)
Neutrophil/Lymphocyte ratio	2.57 ± 1.17
Less than 2.2	20 (48.8)
Not less than 2.2	21 (51.2)
Number of neoadjuvant treatments
2	20 (48.8)
3	17 (41.5)
4	4 (9.7)
Patients’ mismatch repair status
dMMR/MSI-H	0 (0)
pMMR/MSS	41 (100)

BMI: Body mass index; CRM: Circumferential resection margin; EMVI: Extramural vascular invasion; CEA: Carcinoembryonic antigen; MSI-H: Microsatellite instability-high; dMMR: Mismatch repair-deficient; pMMR: Mismatch repair-proficient; MSS: Microsatellite stable.

Table 2 Treatment outcomes and surgical parameters, n (%)

Characteristic	All patients (n = 41)
Clinical T stage after treatment
cT0	4 (9.8)
cT1	2 (4.9)
cT2	8 (19.5)
cT3	23 (56.0)
cT4a	4 (9.8)
Clinical N stage after treatment
cN0	11 (26.8)
cN1	17 (41.5)
cN2	13 (31.7)
NAR
Less than 8	22 (53.7)
8 to 16	10 (24.4)
Not less than 16	9 (21.9)
ORR	35 (85.4)
DCR	41 (100)
CR	4 (9.8)
PR	31 (75.6)
SD	6 (14.6)
PD	0 (0)
Reduced TMN stage
T stage reduction	17 (41.5)
N stage reduction	17 (41.5)
TN stage reduction	10 (24.4)
Pathological T stage
ypT0	11 (26.8)
ypTis	1 (2.4)
ypT1	7 (17.1)
ypT2	10 (24.4)
ypT3	10 (24.4)
ypT4	2 (4.9)
Pathological N stage
ypN0	30 (73.2)
ypN1	9 (21.9)
ypN2	2 (4.9)
PCR	11 (26.8)
TRG classification
TRG 0	11 (26.8)
TRG 1	8 (19.5)
TRG 2	10 (24.4)
TRG 3	12 (29.3)
MPR	19 (46.3)
Resection range
R0	41 (100)
R1	0 (0)

NAR: Neoadjuvant rectal; ORR: Objective response rate; DCR: Disease control rate; CR: Complete remission; PR: Partial response rate; SD: Disease stability rate; DP: Disease progression; PCR: Pathological complete response rate; MPR: Major pathological remission rate; TRG: Tumor regression grade.

Table 3 Adverse events during neoadjuvant therapy, n (%)

Treatment-related adverse events	Grade I-II	≥ grade III	All grade
Hematology related
WBC reduction	7 (17.1)	0 (0)	7 (17.1)
Anemia	5 (12.2)	0 (0)	5 (12.2)
PLT reduction	0 (0)	0 (0)	0 (0)
ALT increase	9 (22.0)	0 (0)	9 (22.0)
AST increase	9 (22.0)	0 (0)	9 (22.0)
Elevated bilirubin	3 (7.3)	0 (0)	3 (7.3)
Renal failure	2 (4.9)	0 (0)	2 (4.8)
Total	21 (51.2)	0 (0)	21 (51.2)
Non hematology
Weak	1 (2.4)	0 (0)	1 (2.4)
Nausea	1 (2.4)	0 (0)	1 (2.4)
Diarrhea	9 (22.0)	0 (0)	9 (22.0)
Constipation	1 (2.4)	0 (0)	1 (2.4)
Rash	2 (4.8)	0 (0)	2 (4.8)
Abdominal pain	0 (0)	0 (0)	0 (0)
Hypothyroidism	1 (2.4)	1 (2.4)	2 (4.8)
Hyperthyroidism	0 (0)	0 (0)	0 (0)
Lumbago	0 (0)	0 (0)	0 (0)
Total	15 (36.6)	1 (2.4)	16 (39.0)

WBC: White blood cell; PLT: Platelets; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 4 Multivariable logistic regression analysis of clinical risk assessment factors

Characteristic	P value	OR	95%CI
BMI before treatment (> 24 kg/m2)	0.06	6.72	1.04-66.3
CRM (threatened)	0.11	5.97	0.732-68.1
Tumor size (> 4 cm)	0.036	6.51	1.23-45.2
Before treatment CEA (> 5 ng/mL)	0.035	0.12	0.01-0.73

BMI: Body mass index; CRM: Circumferential resection margin; CEA: Carcinoembryonic antigen; OR: Odds ratio; CI: Confidence interval.