The jnttrndl of Ot'iLiryngiilofiy. Volume 3.S. Niimher 2. 21106 Reovirus Salvage of Positive Resection Margin A Novel Treatment Adjunct Bradford Mechor, MD, Hadi Seikaly, MD, FRCSC, Kevin Wong, MD, Jason Chau, MD, Richard Vwiera, PhD, DVM, and jeffery R. Harris, MD, FRCSC 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 find- ings 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. Sommaire Hypothese: 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. Materiel et methodes: Nous avons deveioppe notre modele en utilisant la lignee cellulaire SCC-22B dc Puniversite du Michi- gan. La tumeur, bien etablie chez 39 souris, a ete extirpee en laissant un lisere tumora! de 1 mm. l,es soutis ont ensuite ete separees en 5 groupes : 1) controle (aucun traitement) 2} irrigation de reovirus inactives par ultraviolet 3) Ic meme virus inac- tive A ete injecte dans la tumeur rcsiduelle et autour de la tumeur 4) iniection de reovirus actif dans et autour de la tumeur residuelle et 5] irrigation avec le virus actif. Les souris ont ete suivies durant 2S semaines et sacrifices. Resultats: Pour les groupes avec irrigation, la tumeur est reapparue chez tous les patients des groupes controle (1 et 2). Les souris traitees par irrigation avec le virus actif tint recidivc dans 3 des 14 sites (217ti), une diffc^rence statistiquement significa- tive (p<.OOi). Quant a I'injection, toutes les souris du groupe controle (3) ont recidive contre seulement 6 des 16 sites dans le groupe injecte avec le virus actif (38%). Cette difference est aussi significative. (p<.007). Conclusion: Un traitement ajuvant par irrigation de reovirus est une nouvelle strategie securitaire et effieace pour ameiiorer le controle local dans un modele murin de carcinome epidermoide humain extirpc avec des marges positives. Key words: injection, irrigation, mouse model, positive tnargin, reovirus , squamous cell carcinoma 97