Current status of high linear energy transfer irradiation.

Based on laboratory investigations, high linear energy transfer (LET) particle irradiation is capable of more efficient cell kill than that associated with conventional or low LET irradiation. The advantages of high LET irradiation include: (1) a greater ability to damage hypoxic cells; (2) a lesser ability for repair of sublethal and potentially lethal radiation-induced damage; (3) less variation in radiation sensitivity relative to the cell cycle; and (4) a greater ability to deposit the radiation dose in the region of the tumor as opposed to the normal surrounding tissue (neutrons do not have this advantage compared to other particle therapy). Despite these laboratory advantages, it has been difficult to demonstrate any advantage of high LET irradiation in the clinic. A number of new developments have occurred to test the role of high LET: (1) sophisticated technology to enable treatment delivery with higher dose rate and improved depth dose; (2) the construction of hospital-based facilities; and (3) the development of randomized studies involving diseases in which the risk of early metastasis is minimized. It is hoped that careful study in the clinic over the next decade will elucidate the role of high LET particle therapy.