PALLIATIVE JAW-SPARING TREATMENT OF A NON-RESECTABLE CANINE ORAL FIBROSARCOMA USING COMBINATION OF ELECTROCHEMOTHERAPY WITH BLEOMYCIN AND IL-12 GENE ELECTROTRANSFER

A 15-year- old male castrated English setter was presented for evaluation of a rapidly growing oral mass. Patient’s history was otherwise unremarkable, except of moderate proteinuria of 5 years duration. Clinical examination findings were within normal limits, except of an ulcerated located at the left mandibular canine tooth, which was histologically confirmed as a high grade infiltrative fibrosarcoma with high mitotic index (61/10 HPF) and multifocal necrotic areas. The client declined full staging, so only hematological and biochemistry examinations of blood were performed, which were without any clinically significant alterations. Furthermore a fine needle aspiration biopsy of regional lymph nodes was performed, which revealed reactive lymphadenopathy without signs of metastases. After declining other more invasive therapeutic procedures, the clients elected treatment with combination of electrochemotherapy and IL-12 electrogene therapy. Four consecutive treatment sessions were performed, resulting not only in complete response of the primary tumor, but also in regression of untreated distant metastasis, which was diagnosed approximately one month after the initial examination.  Furthermore, the percentage of circulating CD8+ cells was increased after each therapy session, indicating possible systemic induction of immune response by IL-12 gene therapy. This case shows that this type of therapy can represent an alternative type of both local and systemic treatment in selected tumor cases, where clients seek a less invasive nonsurgical treatment. Key words: dog; fibrosarcoma; electroporation; electrochemotherapy; electrogene therepy, interleukin-12 PALIATIVNO ZDRAVLJENJE NERESEKTABILNEGA FIBROSARKOMA SPODNJE CELJUSTI PRI PSU S KOMBINACIJO ELEKTROKEMOTERAPIJE Z BLEOMICINOM IN GENSKEGA ELEKTROPRENOSA IL-12 Izvlecek: Petnajstleni kastrirani angleski seter je bil na naso kliniko sprejet z namenom pregleda hitro rastoce novotvorbe v ustni votlini. Pes ni imel pomembnejsih socasnih bolezni, razen zmerne proteinurije zadnjih pet let. Fizikalni pregled ni pokazal nikakrsnih odstopanj z izjemo ulcerirane novotvorbe na podrocju levega mandibularnega grabilca. Histoloska diagnoza novotvorbe je bila infiltrativni fibrosarkom visoke stopnje z visokim mitoticnim indeksom (61/10 v polju visoke povecave) in multifokalnimi nekroticnimi podrocji. Skrbnik psa je zavrnil popolno dolocitev stadija bolezni, zato smo izvedli le osnovne hematoloske in biokemijske preisakve, ki niso pokazale pomembnejsih odstopanj. Izvedli smo tudi tankoligelno biopsijo regionalnih bezgavk, ki je pokazala reaktivno limfadenopatijo brez znakov prisotnosti zasevkov. Po predstavitvi vseh možnosti zdravljenja se je lastnik odlocil za zdravljenje s kombinacijo elektrokemoterapije in genskega elektroprenosa IL-12. Izvedli smo stiri zaporedne cikluse kombinirane terapije, s katero smo dosegli ne le popolni odgovor primarnega tumorja, pac pa tudi regresijo nezdravljenih oddaljenih podkožnih metastaz, ki so se pojavile približno mesec dni po zacetku terapije. Poleg tega smo po vsaki terapiji ugotovili povecan delež cirkulirajocih CD8+ celic, kar lahko nakazuje na to, da je genska terapija z IL-12 sprožila sistemski imunski odziv. Predstavljeni primer kaže, da lahko kombinacija elektrokemoterapije in genskega elektroprenosa IL-12 predstavlja alternativno obliko tako lokalnega kot sistemskega zdravljenja dolocenih novotvorb, zlasti v primerih, ko skrbnik živali želi manj invazivne terapevtske postopke. Kljucne besede: pes; fibrosarkom; elektroporacija; elektrokemoterapija, genski eletroprenos; interlevkin-12