Table 2.

Univariate and multivariate Cox regression analyses for relapse-free survival among 561 primary NF-PanNETs and 196 primary NF-PanNETs of ≤2.0 cm and without lymph node metastases

	Entire NF-PanNET cohort				NF-PanNETs ≤2.0 cm without lymph node metastases
	Univariate Cox regression analysis		Multivariate Cox regression analysis		Univariate Cox regression analysis		Multivariate Cox regression analysis
Patient or tumour characteristics	Relapse-free survival HR (95% Cl)	P value	Relapse-free survival HR (95% Cl)	P value	Relapse-free survival HR (95% Cl)	P value	Relapse-free survival HR (95% Cl)	P value
Gender, female versus male (ref.)	1.354 (0.964 to 1.900)	0.080			1.501 (0.559 to 4.028)	0.420
Age, years*	1.013 (0.999 to 1.027)	0.067			1.034 (0.992 to 1.078)	0.113
Tumour size, >2.0 cm vs ≤2.0 cm (ref.)	3.036 (1.954 to 4.719)	<0.001	2.214 (1.114 to 4.399)	0.023
Tumour size*	1.198 (1.142 to 1.257)	<0.001			4.352 (1.15 to 16.454	0.030	2.251 (0.556 to 9.107)	0.255
Location, head, neck and uncinate vs body and tail/diffuse (ref.)	1.219 (0.873 to 1.704)	0.245			2.244 (0.884 to 5.695)	0.089
WHO grade, G2 or G3 vs G1 (ref.)	3.282 (2.335 to 4.612)	<0.001	1.492 (0.901 to 2.471)	0.120	1.854 (0.596 to 5.772)	0.286
Lymphovascular invasion, presence vs absence (ref.)†	3.562 (2.311 to 5.491)	<0.001	1.057 (0.615 to 1.815)	0.841
Perineural invasion, presence vs absence (ref.)†	3.042 (1.971 to 4.695)	<0.001	1.158 (0.689 to 1.946)	0.580
Tumour stage (pT), pT3 and pT4 vs pT1 and pT2 (ref.)	2.825 (2.020 to 3.951)	<0.001
Lymph node metastasis (pN), pN1 vs pN0 (ref.)‡	4.041 (2.853 to 5.721)	<0.001	2.150 (1.276 to 3.621)	0.004
ARX expression, positive vs negative (ref.)	1.381 (0.921 to 2.071)	0.118			2.584 (0.748 to 8.931)	0.133
PDX1 expression, positive vs negative (ref.)	0.720 (0.508 to 1.019)	0.064			0.880 (0.346 to 2.239)	0.788
Immunophenotype, ARX1+ + DN vs. PDX1+ + DP (ref.)	1.390 (0.981 to 1.968)	0.064			1.137 (0.447 to 2.893)	0.788
ATRX/DAXX expression, loss versus preserved (ref.)	5.144 (3.647 to 7.257)	<0.001			4.199 (1.490 to 11.830)	0.007
ALT, positive versus negative (ref.)	5.650 (3.964 to 8.055)	<0.001	3.514(2.152 to 5.739)	<0.001	5.629 (2.171 to 14.595)	<0.001	4.155 (1.428 to 12.087)	0.009

^*The patient or tumour characteristic of interest was evaluated as a continuous variable.

^†Cox regression analysis is based on data available for 424 of 561 (76%) patients.

^‡Cox regression analysis is based on data available for 502 of 561 (90%) patients.

.ALT, alternative lengthening of telomeres; ARX, aristaless-related homeobox; ATRX, alpha-thalassemia/mental retardation X-linked; DAXX, death domain-associated protein; DN, double negative for ARX and PDX1; DP, double positive for ARX and PDX1; NF-PanNET, non-functional pancreatic neuroendocrine tumour; PDX1, pancreatic and duodenal homeobox 1; ref, reference.