Scoring of linear energy transfer (LET) for calculation of biological dose in proton therapy

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Scoring of linear energy transfer (LET) for calculation of biological dose in proton therapy And why biological calculation should be done within FLUKA Eivind Rørvik May 11, 216 Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 1 / 31

RBE in Proton Therapy Dose [Gy] 3 2 1 Physical dose BED 1.1 BED variable 2 4 6 8 1 12 Depth in Water [cm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 2 / 31

Protons: Constant RBE vs variable RBE (Larsson, 1962) Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 3 / 31

Protoner: Constant RBE vs variable RBE (Paganetti, 215) Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 4 / 31

Linear Energy Transfer Definition Linear Energy Transfer is the energy locally imparted to the medium by a charged particle (de) traversing a distance dl in the medium. LET = de dl Unrestricted LET in Particle Therapy LET = de dl = S Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 5 / 31

Dependency of particle type and energy 1 3 1 2 LET [KeV/µm] 1 1 1 Carbon-12 Proton 1 1 5 1 15 2 25 3 35 4 Particle Energy [MeV/u] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 6 / 31

Mixed field problem - Also from a monoenergetic protons Relative dose [Gy] 1.5 2 4 6 8 1 12 Water equivalent path length [cm] L * f(l) [KeV/µm] 15 1 5 d = cm 1 1 1 1 1 1 2 L [KeV/µm].6.4.2 d = 1 cm 1 1 1 1 1 1 2 L [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 7 / 31

Averages of LET Spectrum Fluence weighted LET (Track LET) f (L) = Dose weighted LET d(l) = Φ(L) Φ(L)dL L LET f f (L) LET f = LET d = Lf (L) dl Ld(L)dL f (L) dl = 1 d (L) dl = 1 Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 8 / 31

Dependency of Dose: S(d) = e αd βd 2 1 RBE = 2Gy.87Gy = 2.29 Survival fraction 1 1 1 2 RBE = 8Gy 5.6Gy = 1.43 X-ray reference 1 3 Protons 2 4 6 8 1 12 Fraction dose [Gy] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 9 / 31

Dependency of LET 1 Survival fraction 1 1 222 KeV/µm γ-ray reference 1 2 33 KeV/µm 94 KeV/µm 24 KeV/µm 13 KeV/µm 2 4 6 8 1 Fraction dose [Gy] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 1 / 31

LET and RBE relationship 12 Dose = 2, Gy 1 8 RBE 6 4 2 1 1 1 1 1 1 2 1 3 1 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 11 / 31

LET and RBE relationship 12 Dose = 4, Gy 1 8 RBE 6 4 2 1 1 1 1 1 1 2 1 3 1 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 12 / 31

LET and RBE relationship 12 Dose = 6, Gy 1 8 RBE 6 4 2 1 1 1 1 1 1 2 1 3 1 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 13 / 31

LET and RBE relationship 12 Dose = 8, Gy 1 8 RBE 6 4 2 1 1 1 1 1 1 2 1 3 1 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 14 / 31

LET and RBE relationship 12 Dose = 1, Gy 1 8 RBE 6 4 2 1 1 1 1 1 1 2 1 3 1 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 15 / 31

Monoenergetic Protons 8 Linear fit 6 RBE α/αx 4 2 5 1 15 2 25 3 35 4 LET [KeV/µm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 16 / 31

Overview LET d Dose d(l) Database BWF RBE average RBE spectrum BED average BED spectrum Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 17 / 31

Proton Bragg Peak Relative dose 1.8.6.4 Physical Dose LET f LET d A 25 2 15 1 Mean LET [KeV/µm].2 5 2 4 6 8 1 12 Water equivalent path length [cm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 18 / 31

Proton Spread out Bragg Peak Relative dose 1.8.6.4.2 Physical Dose LET f LET d B 2 15 1 5 Mean LET [KeV/µm] 2 4 6 8 1 12 Water equivalent path length [cm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 19 / 31

Proton Bragg Peak Physical Dose [Gy] 3.5 3 2.5 2 1.5 1 Physical dose BED 1.1 BED average BED spectrum 3.5 3 2.5 2 1.5 1 Biologisk Dose [GyRBE].5.5 2 4 6 8 1 12 Depth in water[cm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 2 / 31

Proton Spread Out Bragg Peak Physical Dose [Gy] 3.5 3 2.5 2 1.5 1 Physical dose BED 1.1 BED average BED spectrum 3.5 3 2.5 2 1.5 1 Biologisk Dose [GyRBE].5.5 2 4 6 8 1 12 Depth in water[cm] Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 21 / 31

USRYIELD setup Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 22 / 31

The GETLET function Particle type Energy GETLET() LET Material Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 23 / 31

LET scoring in FLUKA Fluence weighted = Fluence FLUSCW D = Φ LET ρ Φ weighted = Φ LET ρ Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 24 / 31

Partly calculation of biological dose Needs implementation of biological model, 3 quantities must be scored: Dose: Alpha term: Squared of Beta term: FLUSCW = LET ρ FLUSCW = LET ρ FLUSCW = LET ρ D α(let ) αd β(let ) βd 2 In analysis after wards, the survival (S(D) = e αd βd2 ), RBE and D RBE can be found. Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 25 / 31

Full calculation of the biological dose Needs implementation of biological model and fraction dose, 1 quantity must be scored: 1 variable must be scored FLUSCW = LET ρ RBE(LET, D fraction ) D RBE Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 26 / 31

Online vs Offline Online Partly Biological Calculation Need N biological models Calculates Alpha and Beta terms Quantities per voxel: 1 + 2*N Full Biological Calculation Need N biological models Also need fraction Dose Quantities per voxel: N Offline Full LET spectra Purely physical Physical dose and LET specter Quantities per voxel: 1-1 Average LET Purely physical Physical dose and dose average LET Quantities per voxel: 2 Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 27 / 31

Dose average LET Models is too simple (Mohan, 216) Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 28 / 31

Same concluction for Carbon ions Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 29 / 31

Work in progress Full implementation of LET based models within FLUKA Implementation of RTSTRUCT in Fluka for biological dose calculation Creating a Dose- and tissue dependent model based on LET spectra Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 3 / 31

Modelling Biological Systems as a physists Eivind Rørvik 4th Fluka Advanced Course and Workshop May 11, 216 31 / 31