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(linear scale) Dose (Gy)

(linear scale) Dose (Gy)

figure 3.2. Log-linear illustration of in vitro radiation survival of a typical human cancer cell line showing an initial shoulder (a cell kill) at lower doses (usually 1-2 Gy) followed by a terminal slope (B-cell kill) at higher doses (>3Gy).

where S = surviving fraction, a = initial "repairable" radiation damage, b = irrepairable radiation damage, and D = ionizing radiation dose measured in grays (Gy).

Interestingly, this two-parameter (a, b) exponential model is reproduced when multiple fractions of ionizing radiation are given to either a normal or malignant cell population if the time interval between radiation doses (fractions) is sufficient to allow for initial radiation damage repair (usually 1-3 hours). However, the differential effects of ionizing radiation on cell kill in a malignant versus a normal cell population are not completely explained by this LQ model or any other mathematical model, as discussed later.

The discussion on radiation interactions at the cellular level so far has concerned sparsely ionizing radiation (low LET), such as produced by photons or high-energy electrons that are generated by linear accelerators used clinically for most cancers treated today. High linear energy transfer (high-LET) radiation can also be used clinically and involves the use of charged particles such as alpha particles and pi mesons. Additionally, intermediate-LET sources such as neutrons and protons are also used clinically, with a recent resurgence of interest in proton radiation therapy in the United States and Japan.8,9 Because of these different LET radiation sources, the parameter of relative biologic effectiveness (RBE) is used in experimental radiation biology and clinical radiation therapy. The RBE is the dose ratio of different LET sources to produce the same biologic effect. Typically, with high- or intermediate-LET radiation, the radiation survival curve has a reduced or absent "shoulder" and a steeper exponential slope. The general explanation of the change in radiation survival (a, b parameters) with use of intermediate- to high- and intermediate-LET radiations compared to low-LET radiation is that the ionizing energy deposition is so dense with high- and intermediate-LET radiations that the DNA damage cannot be repaired as efficiently. There may also be less effect from the oxygenation state of a cell or tissue with high LET. However, as discussed later, the advantage of intermediate- and high-LET radiations in the radiation survival curve may not be easily translated to the clinic, as one must carefully weight the RBE of the tumor and the RBE of normal tissues. Thus, the therapeutic gain for a specific tumor and specific dose-

limiting normal tissues may not be improved with high- or intermediate-LET radiation compared to low-LET radiation. Clinically, this is clearly the case for neutron beam irradiation, based on the past 20 years of human testing. As such, the recent renewed interest in proton beam irradiation should be tempered until prospective clinical data are available for specific patient groups in which proton beam treatments are compared to the standard of use of photons from conventional linear accelerators.9

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