Reovirus Salvage of Positive Resection Margin: A Novel Treatment Adjunct

Abstract

We hypothesized that the use of reovirus as an intraoperative adjunct would improve local control of positive margins in a human squamous cell carcinoma nude mouse model. This study was designed to (1) develop a nude mouse human squamous cell carcinoma positive margin model and (2) assess the effect of adjunct intraoperative treatment with reovirus irrigation and injection on local control of resections with positive margins. We developed a positive margin nude mouse model using the University of Michigan SCC-22B cell line. Established tumours in 39 mice were resected, leaving behind a 1 mm positive margin. The mice were then divided into five treatment groups: (1) no treatment was provided, (2) ultraviolet (UV)-inactivated reovirus was irrigated into the wound bed, (3) UV-inactivated reovirus was injected into the positive margin intratumorally and peritumorally, (4) reovirus was injected into the positive margin intratumorally and peritumorally, and (5) reovirus was irrigated into the wound bed. The mice were followed for 28 weeks and sacrificed. The results of the irrigations showed that tumours recurred in all (100%) of the control groups (no treatment and UV-inactivated virus). The mice irrigated with active reovirus solution had recurrence in 3 of the 14 sites (21%). These findings were statistically significant, with p > .001. The results of the injection showed that tumours recurred in all (100%) of the control groups (no treatment and UV-inactivated virus). The mice injected with reovirus solution had recurrence in 6 of the 16 sites (38%). These findings were statistically significant, with p > .007. Reovirus adjunctive treatment is a novel, safe, and effective method of improving local control in the positive margin human squamous cell carcinoma mouse model.