EFFECTS OF I-125 BRACHYTHERAPY ON THE PROLIFERATIVE CAPACITY AND HISTOPATHOLOGICAL FEATURES OF GLIOBLASTOMA RECURRING AFTER INITIAL THERAPY

OBJECTIVE: To determine the effect of initial therapy (surgery and ext ernal beam radiation) on the proliferative capacity of glioblastoma an d whether adjunctive high focused doses of radiation therapy can furth er reduce the proliferative capacity of the tumor. This would provide a rationale for attempting to further control local tumor growth with the different forms of high-dose focused radiation available. METHODS: Patients with glioblastoma were initially treated within a randomized , controlled study with or without iodine-125 (I-125) brachytherapy af ter initial surgical resection and external beam radiation (50 Gy in 2 5 fractions). Specimens from 24 consecutive patients later reoperated for ''recurrence'' were used to determine the effects of I-125 brachyt herapy on the histological features and proliferating cell nuclear ant igen index of the tumor tissue. RESULTS: I-125 brachytherapy reduced h istological features prognostic for tumor progression, i.e., cellulari ty, pleomorphism, vessel hyperplasia, and degree of mitosis (P < 0.05) . The degree of mitosis (marker for the mitotic or ''M'' phase) and pr oliferating cell nuclear antigen index (marker for the late G1 and S p hase) provide complementary data on the cell kinetics of the tumor. Pr oliferating cell nuclear antigen immunostaining was lower in the I-125 brachytherapy group (34.6 +/- 8.2%, mean +/- standard error) compared with the control nonimplant group (68.2 +/- 3.5%). I-125 brachytherap y produced a dramatic reduction in mitotic figures (mean histological score = 0.0 +/- 0.0). CONCLUSION: Adjunctive treatment of glioblastoma with discrete high doses of radiation therapy delivered by I-125 brac hytherapy allows further control of the proliferative capacity of the tumor.