Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype

Table 1 Comparison of pathological features by CpG island methylator phenotype status

	CIMP-H	CIMP-I	CIMP-L	P value
Mean age	66	69.2	63.9
Sex
Female	5	14	28
Male	16	26	71
ypT stage
0 or pCR	2	2	16
1	3	1	7
2	2	10	20
3	11	24	48
4	3	3	8
ypN stage
0	11	27	65
1	6	8	21
2	4	5	13
Systemic recurrence
Absent	14	30	66
Present	5	2	22
Local recurrence
Absent	20	37	87
Present	0	2	6
EMVI
Negative	13	33	84
Positive	8	7	15	CIMP-L vs CIMP-H P = 0.028
KRAS status
Wildtype	15	20	73
Mutant	6	20	26	KRAS Mut + CIMP-I P = 0.01
CRM
Not involved	21	39	95
Involved	0	0	4
RC path score
1 (pCR)	0	2	12
2	6	9	14
3	15	29	73
Total	21	40	99

CRM: Circumferential resection margin; CIMP: CpG island methylator phenotype; EMVI: Extramural vascular invasion; pCR: Pathological complete response.

Table 2 Tumour regression scores (Royal College Pathologists data set) by extramural vascular invasion status

	EMVI+	EMVI-	P value
RC Path 1 (pCR)	0	14	0.039
RC Path 2	1	28
RC Path 3	29	88

EMVI: Extramural vascular invasion; pCR: Pathological complete response.

Table 3 Multivariable analysis of pathological and molecular variables against overall survival

	Wald statistic	OR	95%CI (lower)	95%CI (upper)	P value
T stage	1.735	1.392	0.851	2.279	0.188
N stage	0.268	0.857	0.479	1.535	0.605
EMVI	9.422	4.041	1.657	9.857	0.002
CIMP status	0.982	0.791	0.498	1.257	0.322
KRAS status	2.162	1.740	0.832	3.640	0.141
Sex	0.439	0.764	0.344	1.695	0.508
Local recurrence	0.861	1.763	0.532	5.839	0.353
Systemic recurrence	2.165	1.729	0.834	3.584	0.141
Tumour regression (pCR)	0.052	0.793	0.109	5.785	0.819
Involved CRM	0.146	1.339	0.299	6.002	0.703

CRM: Circumferential resection margin; CIMP: CpG island methylator phenotype; EMVI: Extramural vascular invasion; pCR: Pathological complete response.

Table 4 Binary logistic regression analysis; extramural vascular invasion positivity against overall survival and other pathological, demographic and molecular features

	OR	95%CI (lower)	95%CI (upper)	P value
Overall survival	0.936	0.893	0.981	0.006
T stage	7.764	1.749	34.463	0.007
N stage	2.552	0.851	7.651	0.095
Age	1.024	0.969	1.081	0.405
Systemic recurrence	0.865	0.200	3.749	0.846
Sex	0.564	0.119	2.668	0.470
Local recurrence	1.841	0.193	17.562	0.596
Involved CRM	0.276	0.009	8.376	0.459
KRAS mutation	1.577	0.389	6.391	0.524
CIMP-H	6.368	1.091	37.162	0.040

CRM: Circumferential resection margin; CIMP: CpG island methylator phenotype.