Last modified on 9 April 2014, at 14:21

Radiation Oncology/Radiobiology/Linear-Quadratic



Linear-Quadratic Formalism


Linear-quadratic modelEdit

  • A model which describes cell killing, both for tumor control and for normal tissue complications
  • Most common underlying biological rationale is that radiation produces a double strand DNA break (DSB) using a single radiation track
  • Individual DSB can be repaired, with first order kinetics and half-life T1/2
  • If more than one unrepaired DSB is present in the cell at the same time (arising from two separate radiation tracks), a misjoining can produce a lethal lesion (e.g. dicentrics)
  • The two separate DSB can happen at different times during treatment, allowing for repair of first DSB prior to misjoining with the second DSB
  • A single radiation track can also give rise to a lethal lesion by itself (e.g. point mutation in vital gene, deletion eliminating vital gene, induced apoptosis, etc)
  • In the LQ formalism, the yield of lethal lesions is the sum of lethal lesions produced from a single radiation track (which are linearly related to dose, αD) and lethal lesions produced from two radiation tracks (which are quadratically related to dose, βD2)
    • Y = αD + βD2
  • Because the two separate DSB can be repaired prior to resulting in a lethal event, the second component is modified by the Lea-Catcheside time factor (G) to show dependence on dose protraction. For single fractions, G=1
    • Y = αD + GβD2
  • Lethal lesions are thought to follow Poisson distribution from cell to cell. Therefore, the surviving fraction (SF) is
    • SF = exp -(Y)
  • This leads to the standardized LQ equation
    • SF = exp -(αD + GβD2)

Protracted RadiationEdit

SF = \exp -(\alpha D + \beta D^2)

SF = surviving fraction
  • First proposed by Douglas and Fowler in 1972 (PMID 1265229 - Douglas BG and Fowler JF. The effect of multiple small doses of X-rays on skin reactions in the mouse and a basic interpretation. Radiat Res 66, 401-26, 1976.)

E = -ln SF

E = biological radiation effect

ETD = E/\alpha = D[1 + D(\beta/\alpha)] = D \times RE

ETD = extrapolated tolerance dose
D = total dose (Gy)
RE = relative effectiveness per unit dose

For fractionated treatments:
RE = 1 + dn(\beta/\alpha)

dn = dose per fraction (Gy)

For protracted irradiation (constant dose rate):
RE = 1 + (2R/\mu)(\beta/\alpha)\left\{1 - (1/\mu)T\left[ 1 - \exp(-\mu T)\right]\right\}

R = dose rate, LDR (Gy/hr)
\mu = sublethal damage repair exponential time constant (Liters/hr).
\mbox{also, } \mu = \frac{\ln 2}{T_{\tfrac{1}{2}}} \mbox{, where } T_{\tfrac{1}{2}} \mbox{ is the half life of sublethal damage repair}
T = treatment time (hr)

is approximately the same as,

RE = 1 + (2R/\mu)(\beta/\alpha)\left\{1 - (1/\mu)T\right\},
for values of T: 10 hr > T > 100 hr.


  • Glasgow; 1998 PMID 9572622 -- "The linear-quadratic transformation of dose-volume histograms in fractionated radiotherapy." (Wheldon TE, Radiother Oncol. 1998 Mar;46(3):285-95.)
    • Radiobiological transformation of physical DVH to incorporate fraction size effects
    • Outcome: "hot spots" and "cold spots" are further from mean than physical distributions indicate; particularly important in plans with significant dose heterogeneity
    • Conclusion: LQ-DVH should be computed in parallel with conventional DVHs

LQ and High Fractional DoseEdit

  • Duke; 2008 PMID 18725110 -- "The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery." (Kirkpatrick JP, Semin Radiat Oncol. 2008 Oct;18(4):240-3.)
    • Counterpoint argument to PMID 18725109.
    • LQ model does not reflect vascular and stromal damage produced at high doses per fraction, it also ignores impact of radioresistant subpopulations of cells such as cancer stem cells
  • Columbia; 2008 PMID 18725109 -- "The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction." (Brenner DJ, Semin Radiat Oncol. 2008 Oct;18(4):234-9.)
    • Point argument to PMID 18725110
    • Linear quadratic model is reasonably well validated for doses up to 10 Gy/fraction, and could be reasonably used to about 18 Gy/fraction

Extended LQ ModelsEdit

  • Ohio State; 2010 PMID 20610850 -- "A generalized linear-quadratic model for radiosurgery, stereotactic body radiation therapy, and high-dose rate brachytherapy." (Wang JZ, Sci Transl Med. 2010 Jul 7;2(39):39ra48.)
    • Generalized LQ model (gLQ) developed. Compared to in vitro data. Able to extrapolate up to 11-13 Gy from low dose data
  • UT Southwestern; 2008 PMID 18262098 -- "Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy." (Park C, Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):847-52.)
    • Hybridization of two classic radiobiologic models: LQ model and multi-target model. LQ model good for conventionally fractionated therapy; multi-target model good for high (ablative) fractional doses seen in SBRT
    • Allows for easier conversion of doses


ReferencesEdit

  • PMID 8631555 - Liu WS et al. Determination of the appropriate fraction number and size of the HDR brachytherapy for cervical cancer.Gynecol Oncol. 1996 Feb;60(2):295-300.