Reovirus Salvage of Positive Resection Margin: A Novel Treatment Adjunct

Abstract

Hypothesis:We hypnthesized tbat the use of teoviriis as an intraoperativc adjunct would improve local contri)! of positive margins in a human squamous cell carcinotna nude mouse model.Purpose: Tbis study was designed to (1) develop a nude mouse bumaii squamous cell carcinoma positive margin model and (2) assess tbe effect of adjunct intraopctativc treatment with reovirus irrigation and injection nn local conttoj of resections witb positive margins. Materials and Methods:We developed a positive margin nude mouse model using the University of Michigan SCX>22B cell line. Established tumours in 39 mice were resected, leaving bebind a I mm positive margin. The mice were then divided into five treatment gtoups: (1) no treatment was provided., (2) ultraviolet (UV)-inactivated reovirus was irrigated into the wound bed, (3) UV-inactivated reovirus was injected into tbe positive margin intratumorally and pcritumorally, (4) reovirus was injected into the positive margin Intratumorally and peritumorally, and (5) reovirus was irrigated into tbe wound bed. The mice were followed for 28 weeks and sacrificed. Restilts:The results of the irrigations sb{)weci tbat tumours recurred in all (100%) of tbe control groups [no treatment and UV-inactivated virus). The mice irrigated witb active reovirus solution had recurrence in 3 of tbe 14 sites (21%). These findings were statistically significant, with p > .001. The results of the injection showed tbat tumours recurred in all (100%) of the control groups (no treatment and UV-inactivated virus). The mice injected with reovirus solution bad recurrence in 6 of the 16 sites (38%). These findings were statistically significant, with p > .007. Conclusions:Reovirus adjunctive treatment is a novel, safe, and effective method of improving local control in tbe positive margin human squamous cell carcinoma mouse model. SommaireHypothese: Nous avons fait Phypotbese que I'utilisiUion du reovirus comme adjuvant peroperatoire ameliorerait le controle local de tumeur avec tnarge positive dans un modele de carcinome epidermoide chez des souris nues.Objectif: Les buts de cette etude sont: 1) de dcvelopper un modele cbez la souric nue de carcinome epidermoide bumain avec marges positives et 2) d'cvaluer Teffet d'un traitement adjuvant d'irrigation peroperatoire avec reovirus sur Ic conrrole local du meme modele.

Oncolytic activity of reovirus in HPV positive and negative head and neck squamous cell carcinoma

“…Reovirus was first shown to have an oncolytic effect in head and neck cancer cells by Ikeda et al [ 22 ] using in vitro and in vivo models. This effect has been demonstrated in numerous head and neck cell lines [ 24 , 25 , 36 , 37 ]. The oncolytic effect is believed to be independent of epidermal growth factor receptor (EGFR) activation and molecular predictors of response have yet to be identified [ 25 ].…”

“…Preclinical studies have shown the effectiveness of a combination of reovirus, paclitaxel and cisplatin in head and neck cancer lines [ 24 ]. Also, animal models have suggested a role for reovirus as an adjunct in surgically resected disease with positive margins [ 37 ]. Intravenously administered reovirus in combination with carboplatin and paclitaxel has been shown to have activity in advanced stage and recurrent head and neck cancer in a recently published phase I/II clinical trial [ 35 ].…”

“…Susceptibility of HNSCC cells towards reovirus infection and reovirus-induced cell death has been previously demonstrated in both in vitro and mouse models [ 22 , 26 , 36 , 37 ], but the effectiveness and infectivity of reovirus in HPV positive and negative head and neck cancer cell lines has not been examined. The objectives of this study were to compare the infectivity and oncolysis of reovirus in HPV positive and negative HNSCC cell lines.…”