Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1(R132H), were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1(R132H)-positive and 1 control IDH1(R132H)-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1(R132H)-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1(R132H)-negative GBM variants, an IDH1(R132H)-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1(R132H)-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.