Radiobiology of Stereotactic Body Radiation Therapy/Stereotactic Radiosurgery and the Linear-Quadratic Model

Abstract

Received Feb 26, 2013, and in revised form Mar 11, 2013. Accepted for publication Mar 12, 2013The validity of the linear-quadratic (LQ) model for calculatingisoeffect doses in radiation therapy has been intensivelydebated in recent issues of the International Journal of Radi-ation Oncology, Biology, Physics (1-3).TheLQmodelissimple and convenient, and by far it has been the most usefulmeans for isodose calculation in treating tumors with conven-tional fractionated radiation therapy (2-4). The LQ modelsolely depends on the expected incidence of direct interactionsof radiation with specific cellular targets (ie, DNA strands).Because the LQ survival curve continuously bends downwardwith increasing radiation dose, many assume that the LQcalculation will inherently overestimate cell death caused byhigh-dose-per-fraction radiation therapy. Interestingly, however,clinical results have shown that the LQ model actually under-estimates tumor control by stereotactic body radiation therapy(SBRT) or stereotactic radiosurgery (SRS) (5), indicating thatmechanism(s) in addition to DNA strand breaks and/or chro-mosome aberrations may be involved in response of tumors toSBRT or SRS. Therefore, it has been hypothesized that SBRTor SRS may cause significant vascular damage in tumors,leading to indirect cell death (5, 6). We have recently reviewedprevious studies on the radiation-induced vascular damage intumors and pointed out the potentially important role of indi-rect/necrotic cell death due to the vascular damage in tumorcontrol with SBRT and SRS (7). We further discussed theradiobiological principles of SBRT and SRS in relation toradiation-induced vascular damage and resultant indirect celldeath (8). Interestingly, some 35 years ago we (C.W.S. andS.H.L.) realized that irradiation of rodent tumors with 10-20Gy in a single dose caused severe vascular injury, leading tonecrotic cell death in significant fractions of tumor cells 2 to 3days after the treatment (9, 10). Figure 1 summarizes theobservations we made on the effects of 10 Gy (1000 rads) ofx-rays in a single dose on the clonogenic surviving cells inWalker 256 rat tumors (10). The surviving cell fraction, asmeasured with an in vivoein vitro excision method, wasapproximately 2.6 10