Implications for clinical treatment from the micrometer site dosimetric calculations in boron neutron capture therapy

Boron neutron capture therapy has now been used for several malignancies. Most clinical trials have addressed its use for the treatment of glioblastoma multiforme. A few trials have focused on the treatment of malignant melanoma with brain metastases. Trial results for the treatment of glioblastoma multiforme have been encouraging, but have not achieved the success anticipated. Results of trials for the treatment of malignant melanoma have been very promising, though with too few patients for conclusions to be drawn. Subsequent to these trials, regimens for undifferentiated thyroid carcinoma, hepatic metastases from adenocarcinoma of the colon, and head and neck malignancies have been developed. These tumors have also responded well to boron neutron capture therapy. Glioblastoma is an infiltrative tumor with distant individual tumor cells that might create a mechanism for therapeutic failure though recurrences are often local. The microdosimetry of boron neutron capture therapy can provide an explanation for this observation. Codes written to examine the micrometer scale energy deposition in boron neutron capture therapy have been used to explore the effects of near neighbor cells. Near neighbor cells can contribute a significantly increased dose depending on the geometric relationships. Different geometries demonstrate that tumors which grow by direct extension have a greater near neighbor effect, whereas infiltrative tumors lose this near neighbor dose which can be a significant decrease in dose to the cells that do not achieve optimal boron loading. This understanding helps to explain prior trial results and implies that tumors with small, closely packed cells that grow by direct extension will be the most amenable to boron neutron capture therapy.