INVESTIGATION OF THE IMPACT OF ADVANCED MODELS

FOR THE COMPUTATION OF CARBON ION DOSE

DANIEL SIMON COLOMAR
SEPTEMBER 2019 – FEBRUARY 2020
SUPERVISORS: NIELS BASSLER, LARS GLIMELIUS (EXTERNAL), ELIAS CONIAVITIS (EXTERNAL)
CONTENTS

1. Introduction
2. Theoretical background
3. Physical dose computation. Nuclear interaction correction.
4. Biological dose computation. Trichrome.
5. Conclusion.
 1.
INTRODUCTIO
N
1. INTRODUCTION

 Radiotherapy: Cancer treatment method where

ionizing particles are targeted to a tumor tissue.
 First proposition: Wilhelm Röntgen, 1895, X-rays.

 Biological effects proportional to dose [J ∙ kg]

  Ion therapy: why?



 Treatment planning

 Purpose of this thesis: investigate two algorithms

for more accurate carbon dose computation:
Nuclear interaction correction and trichrome.

Image source: Weyrather and Debus, 2003

 2.
THEORETICAL
BACKGROUND
2. THEORETICAL BACKGROUND

 When a charged particle travels through a medium, it may interact with the medium in the following ways:
 Inelastic interactions with electrons of the medium.
 Elastic interactions with nuclei of the medium.
 Inelastic nuclear interactions with nuclei of the medium (nuclear reactions)
2. THEORETICAL BACKGROUND. STOPPING POWER.

 Energy loss per unit distance: stopping power.

 At therapeutic energies, given by the Bethe Bloch formula.

 Most prominent characteristic: inverse square dependence

with particle velocity – Bragg peak
 Depth at which the Bragg peak occurs depends on
initial particle energy.

Dose produced by a 252 MeV/u carbon ion beam in water

2. THEORETICAL BACKGROUND. INTERACTIONS WITH NUCLEI.

 Elastic interactions with nuclei of the medium: produces changes in the trajectory of the ion projectiles.

 Multiple events at the beam line, producing a radial spread of the ions (Multiple Coulomb Scattering, MCS)

 In analytical carbon ion dose calculation, described by Fermi-Eyges theory.

 In practice, this means that the transversal distribution of the dose is described by a Gaussian.

 Inelastic interactions with nuclei of the medium: nuclear reactions

 Atomic fragmentation: secondary fragments are produced.

 In practice, described by adding additional wider Gaussians than the MCS Gaussian.

 Carbon ion attenuation can be described by the following formula (Kanematsu et al, 2013)
2. THEORETICAL BACKGROUND. INTERACTIONS WITH NUCLEI.

Number of fragments per primary particle Fit of the RayStation nuclear halo to FLUKA measurements
for a 300 MeV/u carbon ion beam at the Bragg peak of a 300 MeV/u carbon ion beam
2. THEORETICAL BACKGROUND. SOBP.

 Carbon ion Bragg peak is relatively sharp. However, tumors are

extensive.
 To extend the Bragg peak to an extensive region:
 Modify beam energy so that the sum of doses of every beam yields a
constant dose in the target.
 Steer the beam transversely with

 This delivery technique is called pencil beam scanning.

 Total dose is the weighted sum of all individual beam doses.

3. PHYSICAL DOSE
COMPUTATION.
NUCLEAR
INTERACTION
CORRECTION.
 3. PHYSICAL DOSE COMPUTATION.

 First step: Patient image obtention. Used to define structures and get
the density of the patient at every position.
 In CT images, each pixel is associated with a number in the
Hounsfield scale.
 Image is discretized in a 3D grid: voxels.

 Each voxel is given a unique HU value → density → stopping power

3. PHYSICAL DOSE COMPUTATION. CONCEPTS.

 Integrated depth dose (IDD):

 Radiological depth or water equivalent depth:

3. PHYSICAL DOSE COMPUTATION. PENCIL BEAM ALGORITHM.

 The dose produced by a beam is factorized in an IDD and a transversal dose profile.
3. PHYSICAL DOSE COMPUTATION. PENCIL BEAM ALGORITHM.

 The dose produced by a beam is factorized in an IDD and a transversal dose profile.
3. PHYSICAL DOSE COMPUTATION. PENCIL BEAM ALGORITHM.

 The dose produced by a beam is factorized in an IDD and a transversal dose profile.

If many beams...
3. PHYSICAL DOSE COMPUTATION. PENCIL BEAM ALGORITHM LIMITATIONS.

 Infinite slab approximation.

 Dose in materials is computed as dose in water, using radiological depth. However, nuclear reactions depend on
stochimetric elemental composition, which is not taken into account.
3. PHYSICAL DOSE COMPUTATION. PENCIL BEAM ALGORITHM LIMITATIONS.

 Infinite slab approximation.

 Dose in materials is computed as dose in water, using radiological depth. However, nuclear reactions depend on
stochimetric elemental composition, which is not taken into account.

Nuclear interaction correction

3. NUCLEAR INTERACTION CORRECTION.

 Method to better account for nuclear reactions in materials different to water.

 Based on the work by Inaniwa et al, 2014

 Model implemented in the treatment planning system iDose (developed by NIRS, Japan), currently used clinically.

 In the present work, the model has been implemented in RayStation (RaySearch Laboratories AB) in two different
variants.
3. NUCLEAR INTERACTION CORRECTION. THEORY.
 Nuclear reaction cross section for ions in therapeutic energies (Sihver et al, 1993)

 Probability of a nuclear reaction per path length.

 Relative nuclear reaction probability.

 Water equivalent depth for nuclear reactions.

3. NUCLEAR INTERACTION CORRECTION. THEORY.

 The dose produced by primary carbon ions at a certain depth is

proportional to the number of carbon ions at that depth.
 If no correction is done, the number of carbon ions is taken to be the one
at . However, it would be more correct to take the number of carbon
ions at

1st component: MCS (Primary carbon)

2nd component: Inner halo (Heavy fragments Z ≥ 3)
3rd component: Outer halo (Light fragments Z < 3 )
3. NUCLEAR INTERACTION CORRECTION. THEORY.

 Correction proposed by Inaniwa et al, 2014: Multiply dose by primary carbon ions by , and divide the dose due to
light fragments by .
3. NUCLEAR INTERACTION CORRECTION. THEORY.

 Correction proposed by Inaniwa et al, 2014: Multiply dose by primary carbon ions by , and divide the dose due to
light fragments by .

Primary carbon ions (multiplied) Light fragments (divided)

Heavy fragments (unmodified)

3. NUCLEAR INTERACTION CORRECTION. RESULTS.

Adipose tissue, 252 MeV/u

In adipose, correction predicts

more nuclear interactions.
= less dose due to carbon,
more dose due to fragments.
3. NUCLEAR INTERACTION CORRECTION. RESULTS.

Bone tissue, 252 MeV/u

In bone, correction predicts

less nuclear interactions.
= more dose due to carbon,
less dose due to fragments.
3. NUCLEAR INTERACTION CORRECTION. RESULTS.
3. NUCLEAR INTERACTION CORRECTION. RESULTS.

iDose RayStation
4. BIOLOGICAL
DOSE
COMPUTATION.
TRICHROME.
4. BIOLOGICAL DOSE COMPUTATION.

 Same dose level coming from different particles might have different biological effects (cell killing)

 Clinical experience with photons: it is useful to relate carbon doses to photon doses.

 RBE (ICRU, 1979): “A ratio of the absorbed dose of a reference radiation to the absorbed dose of a test radiation to
produce the same level of biological effect, other conditions being equal“
 In practice, in our case, ratio between carbon ion dose and X-ray photon dose.
4. BIOLOGICAL DOSE COMPUTATION.

 RBE depends on multiple factors:

 Type of irradiating particle
 Type of irradiated tissue
 Oxygenic status of the cell
 Number of fractions dose is delivered
 Etc.

 There have been multiple approaches to model RBE.

 In treatment planning: LEM, MKM

 Let’s not get into the math…

4. BIOLOGICAL DOSE COMPUTATION. TRICHROME.
 Conventionally, monochrome is used: homogeneous distribution of all particle species in the transversal plane.

 Trichrome: Considers three different particle ”colors”: Primary carbon ions, heavy fragments, light fragments.
(Inaniwa and Kanematsu, 2014)
4. BIOLOGICAL DOSE COMPUTATION. TRICHROME. RESULTS.

Transversal dose at a depth of 90% of the Bragg peak depth

Beam energy: 430 MeV/u
4. BIOLOGICAL DOSE COMPUTATION. TRICHROME. RESULTS.

Transversal dose at a depth of 90% of the Bragg peak depth

Beam energy: 430 MeV/u
4. BIOLOGICAL DOSE COMPUTATION. TRICHROME.

iDose RayStation
 5.
CONCLUSION
 W.K Weyrather and J Debus. Particle beams for cancer therapy. Clinical Oncology, 15(1):23 - 28, 2003.

 Nobuyuki Kanematsu, Yusuke Koba, and Risa Ogata. Evaluation of plastic materials for range shifting, range
compensation, and solid-phantom dosimetry in carbon-ion radiotherapy. Medical Physics, 40(4):041724, 2013.
 Nuclear-interaction correction of integrated depth dose in carbon-ion radiotherapy treatment planning. Physics in
Medicine and Biology, 60(1):421 − 435, dec 2014.
 L. Sihver, C. H. Tsao, R. Silberberg, T. Kanai, and A. F. Barghouty. Total reaction and partial cross section calculations in
proton-nucleus (zt ≤ 26) and nucleus-nucleus reactions (zp and zt ≤ 26). Physical Review C, 47:1225 − 1236, mar 1993.
 International Comission on Radiation Units and Measurements (ICRU). Quantitative concepts and dosimetry in
radiobiology. ICRU Report 30, 1979.
 Taku Inaniwa and Nobuyuki Kanematsu. A trichrome beam model for biological dose calculation in scanned carbon-ion
radiotherapy treatment planning. Physics in Medicine and Biology, 60(1):437{451, dec 2014.