Table 3.

Multivariate analysis for disease control and overall survival

		OR for disease control (Predictive value, n = 115)			HR for cancer mortality (Prognostic value, n = 202)
Clinical parameter		OR	95%CI	p value	HR	95%CI	p value
Characteristics
Gender	(female/male)	2.251	0.819–6.186	0.116	0.710	0.496–1.015	0.061
Age	(years)	0.972	0.940–1.005	0.093	1.005	0.992–1.018	0.465
WHO baseline status				0.055			< 0.001
(vs. class 3)	0	2.762	0.160–47.813	0.485	0.108	0.048–0.244	< 0.001
	1	5.790	0.390–85.994	0.202	0.163	0.081–0.328	< 0.001
	2	1.375	0.087–21.632	0.821	0.381	0.196–0.743	0.005
Tumor type				0.803			0.008
(vs. Panc/bil/HCC)	CRC/gastric	1.330	0.227–7.788	0.752	0.673	0.385–1.176	0.164
	Urogenital	0.871	0.108–7.019	0.897	0.412	0.211–0.805	0.009
	Breast/Ovarian	0.874	0.146–5.250	0.883	0.448	0.250–0.804	0.007
	Other type	1.836	0.376–8.956	0.452	0.416	0.248–0.697	0.001
Prev. immune treatmenta (yes/no)	2.249	0.752–6.731	0.147	0.903	0.621–1.313	0.593
Treatments
Virus arming				0.381			0.046
(vs. no transgeneb)	GMCSF	2.158	0.670–6.947	0.197	0.626	0.429–0.914	0.015
	CD40L	2.931	0.450–19.067	0.260	0.623	0.353–1.101	0.103
Concomitant CPAc	(yes/no)	1.925	0.642–5.774	0.242	0.969	0.655–1.432	0.873
Concomitant TMZ d	(yes/no)	0.198	0.036–1.096	0.064	1.415	0.873–2.293	0.159
Serial treatment	(yes/no)	0.640	0.210–1.946	0.431	0.947	0.638–1.406	0.787
Intratumorally > 50%e	(yes/no)	0.361	0.123–1.061	0.064	1.391	0.970–1.994	0.073
HMGB1 baseline	(low/high)	2.618	1.004–6.827	0.049	0.638	0.462–0.881	0.006

^aPrevious immune treatments include established immune-based treatments acting directly on the immune system or via antibody-dependent cell-mediated cytotoxicity: antibody therapy, interferon-alfa, Bacillus Calmette-Guerin (BCG) lavages, and/or stem cell therapies.

^bOne patient (in high HMGB1-baseline group) received oncolytic virus coding for hNIS, a sodium iodide symporter protein,⁴⁵ which is not an immune-modulating protein and thus was not considered as a transgene here.

^cConcomitant low-dose cyclophosphamide (CPA) was administered either metronomically per os, intravenously on the day of virus treatment, or as a combination of these, to reduce regulatory T-cells.²⁸

^dConcomitant low-dose temozolomide (TMZ) was administered concurrently per os to induce autophagy.²²

^eIntratumorally > 50% indicates that patient had injectable lesions present, and over half of the virus dose was given intratumorally. Of note, virus administration intratumorally trended for poor prognosis and negative prediction for disease control. Reason for these trends might include the notion that large bulks of tumor mass which are readily accessible for intratumoral injection could also indicate advanced disease, possibly not optimal for the treatment with oncolytic viruses.

Abbreviations: Panc, pancreatic cancer; Bil, biliary cancer; HCC, hepatocellular carcinoma; CRC, colorectal cancer; GMCSF, granulocyte macrophage-colony stimulating factor; CD40L, CD40-ligand.^{24,26,27,29,30,37,38,41-44,50}