The combination of boron neutron-capture therapy and immunoprophylaxis foradvanced intracerebral gliosarcomas in rats

Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA and GEM is almost inv ariably fatal within a few years after it is diagnosed. Despite current neu rosurgical and radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor cells infiltrate surrounding brain tissues and cause r ecurrent disease. Therefore the combination of neurosurgical and radiothera peutic debulking methods with therapies to inhibit occult GEM cells should improve prognosis. In this study we have combined boron neutron-capture the rapy (BNCT), a novel binary radiotherapeutic treatment modality that select ively irradiates tumor tissue and largely spares normal brain tissue, with immunoprophylaxis, a form of active immunization initiated soon after BNCT treatment, to treat advanced, clinically relevantly-sized brain tumors in r ats. Using a malignant rat glioma model of high immunogenicity, the 9L glio sarcoma, we have shown that about half of the rats that would have died aft er receiving BNCT debulking alone, survived after receiving BNCT plus immun oprophylaxis. Further, most of the surviving rats display immunological-bas ed resistance to recurrent 9LGS growth six months or more after treatment. To our knowledge this study represents the first time BNCT and immunoprophy laxis have been combined to treat advanced brain tumors in rats.