Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies

Table 1 Patient, tumor and treatment characteristics

All cases	N (%)
Sex, n (%)
Male	26 (72.2)
Female	10 (27.8)
Age, yr (median)	52.0
ECOG
0	2 (5.6)
1	30 (83.3)
2	4 (11.1)
Tumor location, n (%)
Stomach	3 (8.3)
Duodenum	3 (8.3)
Colorectal cancer	30 (83.3)
Clinical TNM stage, n (%)
II-III	27(75.0)
IV	9 (25.0)
Lynch syndrome
Yes	16 (44.4)
No	20 (55.6)
No clear	0 (0.0)
MMR and MSI status
Consistent	30 (83.3)
Inconsistent	6 (16.7)

ECOG: Eastern Cooperative Oncology Group; MMR: Mismatch repair; MSI: Microsatellite instability; TNM: Tumor-node-metastasis.

Table 2 Details of the 36 patients with neoadjuvant programmed death protein 1 blockade immunotherapy

No.	Tumor location	Clinical stage	MMR status	MSI status	Courses of ICB	Combined treatment	Surgery	Pathological stage
1	Stomach	T4aN2M0	dMMR	MSI-H	Sintilimab × 6	CapeOX	Total gastrectomy	PCR
2	Stomach	T4aN2M0	dMMR	MSI-H	Sintilimab × 5	CapeOX	Total gastrectomy	PCR
3	Stomach	T4aN2M0	dMMR	MSI-H	Sintilimab × 3	CapeOX	Total gastrectomy	PCR
4	Duodenum	T3N0M0	dMMR	MSI-H	Pembrolizumab × 4	-	cCR	-
5	Duodenum	T3N0M0	dMMR	MSI-H	Pembrolizumab × 6	-	cCR	-
6	Duodenum	T4aN0M0	dMMR	MSI-L	Sintilimab × 8	CapeOX	cCR	-
7	LACC	T4aN+M0	dMMR	MSI-H	Pembrolizumab × 2	-	Colectomy	PCR
8	LACC	T3N+M0	dMMR	MSI-H	Sintilimab × 2	-	Colectomy	ypT3N0
9	LACC	T4bN2M0	dMMR	MSI-H	Pembrolizumab × 2	-	Colectomy	PCR
10	LACC	T3N+M0	dMMR	MSI-H	Camrelizumab × 4	CapeOX	Colectomy	PCR
11	LACC	T4bN+M0	dMMR	MSI-H	Pembrolizumab × 1	-	Colectomy	ypT3N0
12	LACC	T3N+M0	dMMR	MSI-H	Camrelizumab × 3	-	Colectomy	ypT2N0
13	LACC	T4bN2bM0	dMMR	MSI-H	Sintilimab × 4	-	Colectomy	ypT1N1b
14	LACC	T4bN+M0	dMMR	MSI-H	Pembrolizumab × 2	-	Colectomy	PCR
15	LACC	T4aN+M0	dMMR	MSS	Sintilimab × 3	CapeOX	Colectomy	ypT3N0
16	LACC	T4aN+M0	dMMR	MSI-H	Toripalimab × 8	-	Colectomy	ypT2N0
17	LACC	T3N0M0	dMMR	MSI-H	Pembrolizumab × 4	-	Colectomy	ypT3N0
18	LACC	T4bN2aM0	dMMR	MSI-H	Sintilimab × 5	-	Colectomy	PCR
19	LACC	T4bN2bM0	dMMR	MSI-H	Sintilimab × 3	-	Colectomy	PCR
20	LACC	T4aN2bM0	dMMR	MSS	Pembrolizumab × 3	-	Colectomy	ypT3N1a
21	LACC	T3N2aM0	pMMR	MSI-H	Pembrolizumab × 3	-	Colectomy	PCR
22	LACC	cT4aN2M0	dMMR	MSI-H	Pembrolizumab × 4	-	Colectomy	PCR
23	Low rectum	T3N1M0	dMMR	MSI-H	Pembrolizumab × 1	-	CCR	-
24	Low rectum	T3N2M0	dMMR	MSI-H	Nivolumab × 3	CapeOX	LAR	PCR
25	Low rectum	T3N+M0	pMMR	MSI-H	Sintilimab × 4	-	LAR	ypT3N0
26	Low rectum	T3N+M0	dMMR	MSI-H	Pembrolizumab × 2	-	CCR	-
27	Low rectum	T3N2M0	pMMR	MSI-H	Camrelizumab × 3	CapeOX	CCR	PCR
28	CLM	M1a	dMMR	MSI-H	Sintilimab × 6	CapeOX	Hepatectomy	PCR
29	CLM	T4bN2M1a	dMMR	MSI-H	Sintilimab × 4	CapeOX	ColectomyHepatectomy	ypT4bN1aM0
30	CLM	M1a	dMMR	MSI-H	Sintilimab × 26	-	CCR	-
31	CLM	T4aN2M1a	dMMR	MSI-H	Pembrolizumab × 4	-	ColectomyHepatectomy	PCR
32	Rectum	T4bN2M1c	dMMR	MSI-H	Pembrolizumab × 1	-	Colectomy	ypT4bN2aM1c
33	Rectum	T4bN2M1a	dMMR	MSI-H	Sintilimab × 6	-	Hartmann	PCR
34	Colon	T4bN2M1c	dMMR	MSI-H	Tislelizumab × 8	-	Colectomy	ypT0N0M1c
35	Colon	T4bN2M1c	dMMR	MSI-H	Sintilimab × 5	CapeOX	Colectomy	ypT3N0M1c
36	Colon	T4aN1M1c	dMMR	MSI-H	Sintilimab × 5	-	Colectomy	PCR

cCR: Clinical complete response; LACC: Locally Advanced Colon Cancer; pMMR: Proficient mismatch repair; dMMR: Different mismatch repair; ICB: Immune checkpoint inhibitor; CLM: Colorectal Liver Metastases; LAR: Low Anterior Resection; PCR: Polymerase chain reaction.

Table 3 Adverse events

Adverse events	No. of patients (%)	No. of patients (%)	No. of patients (%)
Immuno-related	Grade 1	Grade 2	Grade 3
Any	4 (11.1)	4 (11.1)	2 (5.6)
Dermatologic
Rash	2 (5.6)	0 (0)	0 (0)
RCCEP	1 (2.80)	0 (0)	0 (0)
Endocrine
Hypothyroidism	2 (5.6)	2 (5.6)	1 (2.80)
Hyperglycemia	0 (0)	0 (0)	0 (0)
Fatigue	3 (8.3)	4(11.1)	0 (0)
Surgery-related
Any	1 (2.80)	4(11.1)	1 (2.80)
Chylous fistula	0 (0)	2 (5.6)	0 (0)
Anastomosis leakage	0 (0)	2 (5.6)	0 (0)
Fever	1 (2.80)	0 (0)	0 (0)
Intra-abdominal hemorrhage	0 (0)	0 (0)	1 (2.80)

RCCEP: Reactive cutaneous capillary endothelial proliferation.

Table 4 Details of the 6 patients with inconsistency of dMMR and MSI-H

No.	Tumor location	Clinical stage	Heredity	MMR (IHC)biopsy	MMR (NGS) biopsy	MSI (PCR) biopsy	MSI (NGS) biopsy	MMR (IHC) surgery	MMR (NGS) surgery	MMR (PCR) surgery	MMR (NGS) surgery	Reason
6	Duodenum	T4aN+M0	Lynch	dMMR	dMMR	MSI-L	MSI-L					-
15	Colon	T4aN+M0	No	dMMR	pMMR	MSS	MSS	pMMR	pMMR	MSS	MSS	Tumor heterogeneity
20	Colon	T4aN2bM0	No	dMMR	dMMR	MSS	MSS	dMMR	dMMR	MSI-H	MSI-H	Low tumor content
21.	Colon	T3N2aM0	No	pMMR	dMMR	MSI-H	MSI-H					Only MSH3 mt
25	Rectum	T3N+M0	No	pMMR	pMMR	MSS	MSI-H	pMMR	pMMR	MSS	MSI-H	DDR mt
27	Rectum	T3N2M0	No	pMMR	pMMR	MSS	MSI-H					DDR mt

IHC: Immunohistochemistry; PCR: Polymerase chain reaction; NGS: Next-generation sequencing; MSH-L: Microsatellite instability-low; pMMR: Proficient mismatch repair; dMMR: Different mismatch repair; WT: Wild type; MT: Mutant type.