Boron Neutron Capture Therapy for glioblastoma multiforme: advantage of prolonged infusion of BPA-f.

OBJECTIVES: To assess possible improved efficacy of Boron Neutron Capture Therapy (BNCT) for glioblastoma multiforme (GBM) using prolonged infusion and a correspondingly higher dose of l-boronophenylalanine, as the fructose complex (BPA-f). MATERIALS AND METHODS: The benefit of prolonged infusion was analyzed by comparing the results from a Phase II study using 6 h infusion of BPA-f with those obtained from a Phase I/II study using 2 h of infusion. Median survival time (MST) from diagnosis, patient baseline characteristics, salvage treatment and severe adverse events were considered in the comparison. RESULTS: MST increased significantly, from 12.8 (95% confidence interval or CI: 10.3-14.0) months with 2 h infusion to 17.7 (95% CI: 13.6-19.9) months with 6 h of infusion. The fraction of patients with WHO grade 3-4 adverse events was similar in the two studies at 13% and 14%, respectively. CONCLUSION: Prolonged infusion was found to be beneficial for the efficacy of BNCT and it is suggested that 6 h infusion of BPA-f should be used in future trials of BNCT for GBM. BNCT, which is a single-day treatment with mild side effects, should be assessed in a controlled trial, as an alternative to 30 daily fractions of conventional fractionated photon therapy over a period of 6 weeks.

The influence of insurance status on treatment and outcomes in oral cavity cancer: an analysis on 46,373 patients.

The purpose of this study was to determine the influence of insurance status on treatment and outcomes in oral cavity cancer. Patients were identified in the National Cancer Database (NCDB). Data were collected and analyzed using χ2 tests, Kaplan-Meier methods, and multivariable Cox regression models. Those uninsured or on Medicaid were more likely to be younger (P<0.001), minority race (P<0.001), have a lower median household income (P<0.001), lower educational attainment (P<0.001), not undergo primary resection (P<0.001), present with higher T (P<0.001),N (P<0.001), and M (P<0.001) stage of disease, and have a higher tumor grade (P<0.001). On univariate analysis, those with private insurance had significantly better overall survival than those uninsured (hazard ratio (HR) 1.481), under Medicaid (HR 2.006), or on Medicare (HR 1.921). On multivariable Cox regression analysis, insurance status remained an independent prognosticator even after accounting for multiple demographic, socioeconomic, treatment, and clinicopathological factors. These data suggest that insurance status is associated with treatment and outcomes in patients with oral cavity cancer. Being uninsured or on Medicaid was found to be associated with a higher risk of a poorer prognosis when compared to private insurance, and the data suggest the need to expand comprehensive medical coverage and optimize access to adequate medical care in vulnerable patient populations.

Models for estimation of the (10)B concentration after BPA-fructose complex infusion in patients during epithermal neutron irradiation in BNCT.

PURPOSE: To create simple and reliable models for clinical practice for estimating the blood (10)B time-concentration curve after p-boronophenylalanine fructose complex (BPA-F) infusion in patients during neutron irradiation in boron neutron capture therapy (BNCT). METHODS AND MATERIALS: BPA-F (290 mg BPA/kg body weight) was infused i.v. during two hours to 10 glioblastoma multiforme patients. Blood samples were collected during and after the infusion. Compartmental models and bi-exponential function fit were constructed based on the (10)B blood time-concentration curve. The constructed models were tested with data from six additional patients who received various amounts of infused BPA-F and data from one patient who received a one-hour infusion of 170 mg BPA/kg body weight. RESULTS: The resulting open two-compartment model and bi-exponential function estimate the clearance of (10)B after 290 mg BPA/kg body weight infusion from the blood with satisfactory accuracy during the first irradiation field (1 ppm, i.e., 7%). The accuracy of the two models in predicting the clearance of (10)B during the second irradiation field are for two-compartment model 1.0 ppm (8%) and 0.2 ppm (2%) for bi-exponential function. The models predict the average blood (10)B concentration with an increasing accuracy as more data points are available during the treatment. CONCLUSION: By combining the two models, a robust and practical modeling tool is created for the estimation of the (10)B concentration in blood after BPA-F infusion.

Boron neutron capture therapy for malignant gliomas.

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumour tissue. Boron-10 nuclei capture slow 'thermal' neutrons preferentially and, upon capture, promptly undergo 10B(n,alpha)7Li reaction. The ionization tracks of energetic and heavy lithium and helium ions resulting from this reaction are only about one cell diameter in length (approximately 14 microm). Because of their high linear energy transfer (LET) these ions have a high relative biological effectiveness (RBE) for controlling tumour growth. The key to effective BNCT of tumours, such as glioblastoma multiforme (GBM), is the preferential accumulation of boron-10 in the tumour, including the infiltrating GBM cells, as compared with that in the vital structures of the normal brain. Provided that a sufficiently high tumour boron-10 concentration (approximately 10(9) boron-10 atoms/cell) and an adequate thermal neutron fluence (approximately 10(12) neutrons/cm2) are achieved, it is the ratio of the boron-10 concentration in tumour cells to that in the normal brain cells that will largely determine the therapeutic gain of BNCT.