Support for the heavy ion therapy at GSI
The heavy ion therapy project at GSI is a joint project of the University Clinic in Heidelberg, of the DKFZ, of the Gesellschaft für Schwerionenforschung in Darmstadt and of the Forschungszentrum Rossendorf. The advantage of heavy ions for the use in radiotherapy is their higher physical selectivity due to the inverted depth dose profile (Bragg peak) and the higher biological effectiveness in the Bragg-Peak as compared to the entrance region. At GSI, a Carbon ion beam is available for patient treatment during three periods of 4 weeks per year. Since 1997, more than 250 patients, mostly with brain tumours, have been treated using the intensity controlled rasterscan technique with active energy variation. The DKFZ is responsible for the Medical Physics issues of the patient treatments including patient positioning, treatment planning and dosimetry. Encouraging clinical results lead to the construction of a hospital-based facility (Heidelberger Ionenstrahlen-Therapie, HIT) at the University Clinic in Heidelberg which will be completed at the end of 2006.
Development of quality assurance tools
Fig. 1. The system used for treatment plan verification (upper part) and a result of a verification measurement (lower part).
© dkfz.de
Prior to the start of clinical operation at GSI several new methods for dosimetry and quality assurance had to be developed. These were included in a comprehensive quality assurance program which was the basis for the legal approval and was routinely performed during clinical operation since then.
One important example for a new developed method is the dosimetry-system used for treatment plan verification. It consists of a water phantom, in which an array of 24 ionization chambers is moved to the region to be measured. Visualization of the ionization chamber positions within the dose distribution, the movement of the array, measurement, and comparison with the calculated dose values is done with a software interface (fig. 1). To apply the system also in combination with a rotating heavy ion gantry, which will be available at the clinical heavy ion facility in Heidelberg, a motorized solid state phantom is currently under development, which will replace the water phantom.
Radiation response to heavy ions
Fig. 2. a) Dose response curves for single dose irradiations of the rats’ spinal cord with photons and Carbon ions, respectively (biological endpoint: myelopathy). b) RBE of single-dose Carbon ion irradiations of the rat brain as a function of dose (endpoint: MRI-visible changes).
© dkfz.de
Heavy ions show an enhanced relative biological effectiveness (RBE), which is higher in the Bragg-peak (i.e. where the tumor is) than in the entrance region (i.e. in normal tissue). As dose prescription refers to biological effective dose (=Dose [Gy] x RBE), the RBE has to be introduced into treatment planning. A radio-biological model (the local effect model, developed at GSI) is therefore applied to estimate the RBE at each point within the patient.
As there are rather large uncertainties in the knowledge of the RBE for clinical situations, animal models are used to evaluate the accuracy of the model-predictions and their systematic behavior with fraction number and dose per fraction. In these experiments, groups of animals are treated at different dose levels and the probability for the occurrence of selected biological effects (endpoints) is recorded. From these incidence data, dose response curves are derived. As reference for the RBE-determination, the experiments were also carried out with photons.
These investigations are of high clinical relevance and aim to determine the tolerance dose TD50, the fractionation parameter of the linear-quadratic model alpha/beta and the RBE of Carbon ions. The following normal tissues and tumors are under investigation:
- As a model for the central nervous system, the cervical spinal cord of rats was irradiated with Carbon ions in the plateau-region as well as in a spread-out Bragg-peak (SOBP). Occurrence of clinical myelopathy was selected as biological endpoint (fig. 2). The experiments were performed with 1, 2, 6 and 18 fractions.
- To investigate the potential influence of the tissue-structure on the RBE, the experiments were also carried out for focal irradiation of one hemisphere of the rat brain, using radiosurgery–techniques and changes in magnetic resonance imaging (MRI) as biological endpoint.
- To determine the radiobiological parameters for the prostate, an experimental prostate-tumor in the rat is irradiated using a SOBP and several fractionation schemes.
Cooperations
- Research Group Heavy Ion Therapy (Group Leader: PD Dr. O. Jäkel), Dept. of Medical Physics in Radiation Oncology, DKFZ, Heidelberg, Germany
- Collaborators of the Heavy Ion Therapy Project at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, Germany
- Prof. Dr. Dr. J. Debus, PD Dr. D. Schulz-Ertner, Dept. of Radiation Oncology and Radiotherapy, University Clinic Heidelberg, Germany
- Dr. W. Enghardt, Forschungszentrum Rossendorf, Germany
- Dr. P. Peschke, Clinical Kooperation Unit Radiation Oncology, DKFZ, Heidelberg, Germany
Selected References
- Schulz-Ertner D., Nikoghosyan A., Didinger B., Münter M., Jäkel O., Karger C.P., Debus J.: Therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques. Cancer 2005, (in press)
- Schulz-Ertner D., Nikoghosyan A., Thilmann C., Haberer T., Jäkel O., Karger C.P., Kraft G., Wannenmacher M., Debus J.: Results of carbon ion radiotherapy in 152 patients. International Journal of Radiation Oncology, Biology, Physics 58, 631-640, 2004
- Karger C.P., Hartmann G.H., Jäkel O., Heeg P.: Quality management of medical physics issues at the German heavy ion therapy project. Medical Physics 27, 725-736, 2000
- Karger C.P., Hartmann G.H., Heeg P., Jäkel O.: A method for determining the alignment accuracy of the treatment table axis at an isocentric irradiation facility. Physics in Medicine and Biology 46, N19-N26, 2001
- Karger C.P., Jäkel O., Hartmann G.H., Heeg P.: A system for three-dimensional dosimetric verification of treatment plans in intensity-modulated radiotherapy with heavy ions. Medical Physics 26, 2125-2132, 1999
- Karger C.P., Jäkel O., Heeg P., Hartmann G.H.: Klinische Dosimetrie für schwere geladene Teilchen. Zeitschrift für Medizinische Physik 12, 159-169, 2002
- Karger C.P., Münter M.W., Heiland S., Peschke P. Debus J., Hartmann G.H.: Dose response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time. Radiation Research 157, 617-625, 2002
- Karger C.P., Debus J., Peschke P., Münter M.W., Heiland S., Hartmann G.H.: Dose-response curves for late functional changes in the normal rat brain after single carbon-ion doses evaluated by magnetic resonance imaging: influence of follow-up time and calculation of relative biological effectiveness. Radiation Research 158, 545-555, 2002
- Debus J., Scholz M., Haberer T., Peschke P., Jäkel O., Karger C.P., Wannenmacher M.: Radiation tolerance of the rat spinal cord after single and split doses of photons and carbon ions. Radiation Research 160, 536-542, 2003