Treatment Planning and Validation

Group leader: PD Dr. Michael Krämer

This work group studies the interaction of charged particle beams, in particular carbon ions, with matter on multiple scales.

Microscopic calculations

On the microscopic/nanoscopic - scale one has to consider elementary interactions to describe energy and damage deposition. For this purpose, we use the homegrown Monte Carlo code TRAX, which describes the production and transport of secondary electrons produced by heavy ions in matter (Figure 1). Recently, the ability to deal with dose enhancements by heavy atom nanoparticles under ion irradiation has been added (Figures 2).

Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 1
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Figure 1
Figure1
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 2a: Paths of electrons released in a gold nanoparticle by an 80 MeV proton.
GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 2b: Enhancement of the radial dose in the vicinity of the nanoparticle
  • Ref.: Wälzlein C., Scifoni E., Krämer M., Durante M., Simulations of dose enhancement for heavy atom nanoparticles irradiated by protons Phys. Med. Biol., 59 (6):1441-1458 (2014); DOI: 10.1088/0031-9155/59/6/1441

Currently, radiation chemistry is being implemented, mainly aiming at the variation of the Oxygen Enhancement Ratio seen with high LET radiation.

 

 

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Figure 2a: Paths of electrons released in a gold nanoparticle by an 80 MeV proton.
Figure 2b: Enhancement of the radial dose in the vicinity of the nanoparticle
GSI Helmholtzzentrum für Schwerionenforschung GmbH
GSI Helmholtzzentrum für Schwerionenforschung GmbH

Macroscopic dose distribution

On the macroscopic scale, mainly for the purpose of treatment planning, we run a homegrown numerical transport model. It considers electromagnetic and nuclear interactions with empirical corrections for the attenuation of the primary beam as well as for the creation of nuclear fragments. This model is implemented in our treatment planning code, TRiP98. We further use the Local Effect Model (LEM) to calculate and optimize RBE-weighted ("biological') dose distributions (Figure 3).

ichael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 3: IMPT optimized RBE-weighted dose distribution for an adenoid-cystic carcinoma located between the optical nerves.
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Figure 3: IMPT optimized RBE-weighted dose distribution for an adenoid-cystic carcinoma located between the optical nerves.
ichael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH

TRiP98 was in clinical use in the GSI pilot project. Siemens chose it as a prototype for their commercial SynGo PT TPS. Nowadays it serves as a research prototype inside and outside GSI to support new developments in ion beam radiotherapy.Recently support for alternative ions such as 16O and 4He (Figures 4) has been added.

Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 4a: Absorbed dose and RBE as a function of depth for a tumour site between 60 and 100 mm depth, irradiated with a single 4He field
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 4b: Predicted (TRiP98+LEM IV) and measured survival of CHO cells for this 4He plan
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Figure 4a: Absorbed dose and RBE as a function of depth for a tumour site between 60 and 100 mm depth, irradiated with a single 4He field
Figure 4b: Predicted (TRiP98+LEM IV) and measured survival of CHO cells for this 4He plan
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
  • Ref.: Krämer M., Scifoni E., Schuy C., Rovituso M., Tinganelli W., Maier A., Kaderka R., Kraft-Weyrather W.K., Brons S., Tessonnier T., Parodi K., Durante M., Helium ions for radiotherapy? Physical and biological verifications of a novel treatment modality Med. Phys., 43 (4) :1995 -2004 (2016) PMID: 27036594, DOI: 10.1118/1.4944593

Moreover, optimization algorithms have been enhanced with the oxygen enhancement ratio (OER) as a driving force to allow the treatment of hypoxic tumour microenvironments via "kill-painting".

Experimental validation of treatment planning

We do not rely solely on simulations, but regularly perform radiobiological experiments in order to verify our predictions. The classical tools are cellular phantoms such as stacks andthe Biophantom in order to measure one- and twodimensional distributions of cell survival under patient-like conditions (Figures 5).

Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 5a: Biophantom to measure 2D cell survival distributions.
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 5b: Survival of CHO cells measured with the Biophantom and as calculated with TRiP98.
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Figure 5a: Biophantom to measure 2D cell survival distributions.
Figure 5b: Survival of CHO cells measured with the Biophantom and as calculated with TRiP98.
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
  • Ref: Gemmel A., Hasch B., Ellerbrock M., Weyrather W.K., Krämer M., Biological dose optimization with multiple ion fields Phys. Med. Biol., 53 (23):6991-7012 (2008); DOI: 10.1088/0031-9155/53/23/022

A more recent development are the so-called hypoxia chambers, which allow irradiations under controlled oxygen concentrations. This way the "kill-painting" approach could be verified experimentally as a proof of concept (Figures 6).

Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 6a: Experimental setup to verify treatment plans under controlled oxygen conditions
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Figure 6b: Planned and measured survival distributions for OER-optimized plans.
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Figure 6a: Experimental setup to verify treatment plans under controlled oxygen conditions
Figure 6b: Planned and measured survival distributions for OER-optimized plans.
figure 6a
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
Michael Krämer GSI Helmholtzzentrum für Schwerionenforschung GmbH
  • Ref.: Tinganelli W., Durante M., Hirayama R., Krämer M., Maier A., Kraft-Weyrather W.K., Furusawa Y., Friedrich T., Scifoni E., Kill-painting of hypoxic tumours in charged particle therapy; Scientific Reports, 5:Article number: 17016 (2015); DOI: doi:10.1038/srep17016

Main research topics

  •  Macroscopic dose distribution

    • Adaptive treatment planning
    • "Kill-painting" (e.g. to treat hypoxic tumours)
    • Mathematical optimization algorithms
    • Extension of TRiP98 to other ions
    • Extension of TRiP98 to higher (Fair) energies, i.e. in the non-Bragg regime
    • "Space TRiP": could we leverage radiotherapy planning concepts for space applications (very heavy ions, very high energies)?

  •  Microscopic calculations
    •  Low energy electron interactions
    •  Transport in inhomogenous media
    •  Nanoparticles and electron emission from solids
    •  Oxygen Effect
  •   Experimental validation of treatment planning
    •  Verification of 3D dose distributions
    •  Biological verification using 3D cellular phantoms
    •  Biological phantoms with different oxygen concentrations
    •  Tests of adaptive treatment plans

Collaborations

  • DKFZ Heidelberg (Prof. O. Jäkel)
  • HIT Heidelberg (Prof. T. Haberer
  • Uni Marburg (Prof. K. Zink) 
  • Med. Uni Wien (Prof. D. Georg)
  • CNAO Pavia (Prof. S. Rossi)
  • Hochschule Darmstadt (Dept. of Mathematics, Prof. A. Fischer)
  • Uni Aarhus (Dr. Niels Bassler)
  • Uni Namur (Prof. S. Lucas)
  • PTB Braunschweig (Dr. V. Dangendorf)
  • TIFPA/INFN (Prof. Durante, Dr. Scifoni)  
       

Group members

Research scientists:
Dr. Martina Fuß
PostDoc:
Olga Sokol
PhD Student:
Daria Boscolo
Martin Schanz