Biologic Considerations in Targeting Brain tumors for Boron Neutron Capture Therapy
Malignant gliomas and metastatic brain tumors constitute a major group of neoplasms for which there is virtually no effective treatment at the present time. In the United States ~12,000 deaths are attributable to the former and ~ 80,000 – 100,000 to the latter, annually.1 The survival of a group of 1578 patients with primary brain tumors who had been entered into three Radiation Therapy Oncology Group Protocols between 1974 and 1989 has been carefully studied by Curran et al. by means of recursive partitioning analysis.’ Survival was related to the following parameters: 1. age at presentation (<50 versus >50 years) 2. pathologic diagnosis of either astrocytoma with anaplastic foci (AAF) or glioblastoma multiforme (GBM) 3. mental and physical performance status. Using recursive partitioning analysis with amalgamation for the different variables, a series of survival curves were generated that showed very clear differences between those patients who had favorable prognostic indicators i.e. <50 yrs, diagnosis of AAF, high performance status versus those who had unfavorable indicators i.e. >50 yrs, diagnosis of GBM, low performance status. The latter group had median survival times (MeSTs) ranging from 4.6 to 11.1 months and a 2 year survival rate of 9% for those patients with the worst prognostic indicators (classes IV-VI combined) compared to MeSTs of 17.9–58.6 mos and 2 yr survival rate of 55% for those patients who had favorable indicators (class I-III combined). If future clinical trials of BNCT focus on those patients who have the worst prognostic indicators (classes IV-VI), it should be possible to determine in a relatively short time (i.e. 2 years) and with a small group of patients (15–24) if there is therapeutic efficacy, as evidenced by prolongation of survival time (using a test for 2 independent proportions, power 95%, α = 0.05, M.L. Moeschberger, personal communication). The present review will focus on biologic considerations that may be important for targeting both primary and metastatic brain tumors for Boron Neutron Capture Therapy (BNCT).
KeywordsBrain Tumor Malignant Glioma Linear Energy Transfer Boron Neutron Capture Therapy Recursive Partitioning Analysis
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